Rapid pulse electrohydraulic (eh) shockwave generator apparatus and                                                                                                                                                                         methods for medical and cosmetic treatments

ABSTRACT

Apparatuses and methods for electrohydraulic generation of shockwaves at a rate of between 10 Hz and 5 MHz, and/or that permit a user to view a region of a patient comprising target cells during application of generated shockwaves to the region. Methods of applying electro-hydraulically generated shockwaves to target tissues (e.g., for reducing the appearance of tattoos, treatment or reduction of certain conditions and/or maladies).

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.14/773,568 filed Sep. 8, 2015, which is a national phase applicationunder 35 U.S.C. § 371 of International Application No PCT/US2014/021746,filed Mar. 7, 2014, which is a continuation-in-part of U.S. patentapplication Ser. No. 13/798,710, filed Mar. 13, 2013 which claimspriority of U.S. Provisional Patent Application No. 61/775,232, filedMar. 8, 2013. The contents of the above-referenced applications areincorporated into the present specification by reference.

BACKGROUND 1. Field of the Invention

The present invention relates generally to therapeutic uses for shockwaves or shockwaves. More particularly, but not by way of limitation,the present invention relates to an apparatus for generating therapeuticshock waves or shockwaves (shock waves with therapeutic uses).

2. Description of Related Art

Acoustic shockwaves have been used for certain therapies for a number ofyears. “Shock wave” or “shockwave” is generally used to refer to anacoustic phenomenon (e.g., resulting from an explosion or lightning)that creates a sudden and intense change in pressure. These intensepressure changes can produce strong waves of energy that can travelthrough elastic media such as air, water, human soft tissue, or certainsolid substances such as bone, and/or can induce an inelastic responsein such elastic media. Methods for creating shock waves for therapeuticuses include: (1) electrohydraulic, or spark gap (EH); (2)electromagnetic, or EMSE; and (3) piezoelectric. Each is based upon itsown unique physical principles.

A. Devices and Systems for Shockwave Generation

U.S. patent application Ser. No. 13/574,228 (a national-stageapplication of PCT/US2011/021692, which published as WO 2011/091020), byone of the present inventors, discloses a device for producing shockwaves at a high pulse rate using a transducer. That device includes anacoustic-wave generator configured to emit acoustic waves having atleast one frequency between 1 MHz and 1000 MHz; a shockwave housingcoupled to the acoustic-wave generator; and a shockwave medium disposedin the shockwave housing; where the apparatus is configured such that ifthe acoustic-wave generator emits acoustic waves then at least someportion of the acoustic waves will travel through the shockwave mediumand form shock waves. That device can be actuated to form shock wavesconfigured to cause particles within a patient to rupture one or morecells of the patient, and the shock waves can be directed to cells of apatient such that the shock waves cause particles to rupture one or moreof the cells. This acoustic-transducer device can produce high poweredshockwaves at high frequencies or pulse rates.

Other systems for producing shockwaves can include an electrohydraulic(EH) wave generator. EH systems can generally deliver similar levels ofenergy as other methods, but may be configured to deliver that energyover a broader area, and therefore deliver a greater amount of shockwave energy to targeted tissue over a shorter period of time. EH systemsgenerally incorporate an electrode (i.e., a spark plug) to initiate ashock wave. In EH systems, high energy shock waves are generated whenelectricity is applied to an electrode immersed in treated watercontained in an enclosure. When the electrical charge is fired, a smallamount of water is vaporized at the tip of the electrode and the rapid,nearly instantaneous, expansion of the vaporized water creates a shockwave that propagates outward through the liquid water. In someembodiments, the water is contained in an ellipsoid enclosure. In theseembodiments, the shock wave may ricochet from the sides of the ellipsoidenclosure and converge at a focal point that coincides with the locationof the area to be treated.

For example, U.S. Pat. No. 7,189,209 (the '209 patent) describes amethod of treating pathological conditions associated with bone andmusculoskeletal environments and soft tissues by applying acoustic shockwaves. The '209 patent describes that shockwaves induce localized traumaand cellular apotosis therein, including micro-fractures, as well as toinduce osteoblastic responses such as cellular recruitment, stimulateformation of molecular bone, cartilage, tendon, fascia, and soft tissuemorphogens and growth factors, and to induce vascular neoangiogenesis.The '209 patent claims several specific implementations of its method.For instance, the '209 patent claims a method of treating a diabeticfoot ulcer or a pressure sore, comprising: locating a site or suspectedsite of the diabetic foot ulcer or pressure sore in a human patient;generating acoustic shock waves; focusing the acoustic shock wavesthroughout the located site; and applying more than 500 to about 2500acoustic shock waves per treatment to the located site to inducemicro-injury and increased vascularization thereby inducing oraccelerating healing. The '209 patent discloses a frequency range ofapproximately 0.5-4 Hz, and application of about 300 to 2500 or about500 to 8,000 acoustic shock waves per treatment site, which can resultin a treatment duration for each treatment site and/or a “total time pertreatment” for all sites that is inconveniently large. For example, the'209 patent discloses total times per treatment for different examplesranging from 20 minutes to 3 hours.

U.S. Pat. No. 5,529,572 (the '572 patent) includes another example ofthe use of electro-hydraulically generated shockwaves to producetherapeutic effect on tissues. The '572 patent describes a method ofincreasing the density and strength of bone (to treat osteoporosis),comprising subjecting said bone to substantially planar, collimatedcompressional shock waves having a substantially constant intensity as afunction of distance from a shock wave source, and wherein saidcollimated shock waves are applied to the bone at an intensity of 50-500atmospheres. The '572 patent describes the application of unfocussedshock waves to produce dynamic repetitive loading of the bone toincrease mean bone density, and thereby strengthen bone againstfracture. As described in the '572 patent, “the unfocussed shock wavespreferably are applied over a relatively large surface of the bone to betreated, for example to cover an area of from 10 to 150 cm². Theintensity of the shock waves may be from 50-500 atmospheres. Each shockwave is of duration of a few microseconds, as in a conventionallithotripter, and is preferably applied at a frequency of 1-10 shockwaves per second for a period of 5-30 minutes in each treatment. Thenumber of treatments depends on the particular patient.”

U.S. patent application Ser. No. 10/415,293 (the '293 application),which is also published as US 2004/0006288, discloses another embodimentof the use of EH-generated shockwaves to provide a therapeutic effect ontissues. The '293 application discloses a device, system, and method forthe generation of therapeutic acoustic shock waves for at leastpartially separating a deposit from a vascular structure. The '293application describes that the device can produce shockwaves at a pulserate of about 50 to about 500 pulses per minute (i.e., 0.83 to 8.33 Hz)with a number of pulses per treatment site (in terms of per length ofvascular unit being treated) from about 100 to about 5,000 per 1 cm².

B. Shockwave Rate

Prior art literature has indicated that faster pulse rates using EHsystems to provide shockwaves can lead to tissue damage. For example, inone study (Delius, Jordan, & et al, 1988) [2], the effect of shock waveson normal canine kidneys was examined in groups of dogs whose kidneyswere exposed to 3000 shockwaves. The groups differed only in the rate ofshockwave administration which was 100 Hz and 1 Hz, respectively.Autopsy was performed 24 to 30 hours later. Macroscopically andhistologically, significantly more hemorrhages occurred in kidneyparenchyma if shockwaves were administered at a rate of 100 Hz (vs 1Hz). The results showed that kidney damage is dependent on the rate ofshockwave administration.

In another study (Madbouly & et al, 2005) [7], slow shockwavelithotripsy rate (SWL) was associated with a significantly highersuccess rate at a lower number of total shockwaves compared to the fastshockwave lithotripsy rate. In this paper, the authors discussed howhuman studies have also shown a decrease in the incidence of SWL inducedrenal injury or need for anesthesia when slower rates of test SWL wereused.

In yet another study (Gillitzer & et al, 2009) [5], slowing the deliveryrate from 60 to 30 shockwaves per minute also provides a dramaticprotective effect on the integrity of real vasculature in a porcinemodel. These findings support potential strategies of reduced pulse ratefrequency to improve safety and efficacy in extracorporeal shockwavelithotripsy.

C. Tissue as a Viscoelastic Material

One reason for sensitivity to pulse rate found in the prior art may bedue in part to the relaxation time of tissue. Cells have both elasticand viscous characteristics, and thus are viscoelastic materials. Unlikemost conventional materials, cells are highly nonlinear with theirelastic modulus depending on the degree of applied or internal stress.(Kasza, 2007) [6]. One study (Fernandez (2006) [3] suggests thatfibroblast cells can be modeled as a gel having a cross-linked actinnetwork that show a transition from a linear regime to power law strainstiffening.

The authors of another paper (Freund, Colonius, & Evan, 2007) [4]hypothesize that the cumulative shear of the many shocks is damaging,and that the mechanism may depend on whether there is sufficient timebetween shocks for tissue to relax to the unstrained state. Theirviscous fluid model suggested that any deformation recovery that willoccur is nearly complete by the first 0.15 second after the shock. As aresult, their model of the mechanism for cell damage would beindependent of shock rate for shock rates slower than ˜6 Hz. However,actual viscoelasticity of the interstitial material, with a relaxationtime about 1 second, would be expected to introduce its sensitivity tothe shock delivery rate. Assuming the interstitial material has arelaxation time of ˜1 second, the authors would expect significantlydecrease damage for delivery rates lower than ˜1 Hz. Conversely, damageshould increase for faster delivery rates. Implications of their modelare that slowing delivery rates and broadening focal zones should bothdecrease injury.

SUMMARY

Soft tissues may transition from elastic to viscous behavior for pulserates (PRs) between 1 Hz and 10 Hz. As a result, potential damage totissue from shockwaves at PRs between 1 Hz and 10 Hz is unpredictablewhen typical lithotripsy power levels are used. Perhaps as a result, theprior art teaches slower PRs and large total times per treatment (TTPT).For example, currently known EH shockwave systems generally deliver PRsof less than 10 Hz and require large total times per treatment (TTPT)(e.g., TTPT periods of minutes or even hours for even a single treatmentsite). When, as may be typical, a treatment requires repositioning of adevice at multiple treatment sites, the TTPT becomes large andpotentially impractical for many patients and treatment needs.

While long treatment times may be acceptable for extracorporealshockwave lithotripsy, the use of shockwaves to provide non-lithotripsytherapeutic effects on tissue in the medical setting is less thanoptimal if not impractical. For example, the cost of treatment oftenincreases with the time needed to administer a treatment (e.g., due tothe labor, facilities and other resource costs allocated to theadministration of the treatment). Furthermore, in addition to costs, atsome point the duration of providing treatment to the patient becomesunbearable for the patient receiving, and healthcare staff providing,the treatment.

This disclosure includes embodiments of apparatuses and methods forelectrohydraulic generation of therapeutic shockwaves. The presentEH-shockwave systems and methods are configured to deliver shockwaves totissues to provide a predictable therapeutic effect on the tissue, suchas by delivering shockwaves at higher (e.g., greater than ˜10 Hz) toreduce TTPT relative to known systems.

The present embodiments of electrohydraulic (EH) apparatuses can beconfigured to generate high-frequency shock waves in a controlled manner(e.g., using an electrohydraulic spark generator and acapacitive/inductive coil spark generating system). The presentpulse-generation (e.g., electrohydraulic spark circuits) can compriseone or more EH tips and, with the present capacitive/inductive coilspark generating systems, can produce a spark pulse rate of 10 Hz to 5MHz. The shock waves can be configured to impose sufficient mechanicalstress to the targeted cells of the tissue to rupture the targetedcells, and can be delivered to certain cellular structures of a patientfor use in medical and/or aesthetic therapeutic applications.

The present high-pulse rate (PR) shockwave therapies can be used toprovide a predictable therapeutic effect on tissue while having apractical total time per treatment (TTPT) at the treatment site. Thepresent high-PR shockwave therapies can be used to provide a predictabletherapeutic effect on tissue, if the viscoelastic nature of the tissueis considered. Specifically, shockwave therapy utilizing a PR greaterthan 10 Hz and even greater than 100 Hz can be used to provide apredictable therapeutic effect on tissue because at those PRs the tissueis, for the most part, predictably viscous in nature and generally doesnot vary between elastic and viscous states. Given that tissue behavesas a viscous material at great enough PRs, the PR and power level can beadjusted to account for the tissue's viscous properties. When theviscous nature of the tissue is accounted for using higher PRs, lowerpower levels can be used to achieve therapeutic effects. One benefit ofusing higher PRs in combination with lower power levels is the reductionin cavitation formation, which further improves predictability of thepresent shockwave therapies. Embodiments of the present EH apparatusesand methods can provide targeted rupturing of specific cells withoutdamaging side effects such as cavitation or thermal degradation ofsurrounding non-targeted cells.

Some embodiments of the present apparatuses (for generating therapeuticshock waves) comprise: a housing defining a chamber and a shockwaveoutlet; a liquid disposed in the chamber; a plurality of electrodesconfigured to be disposed in the chamber to define one or more sparkgaps; and a pulse-generation system configured to apply voltage pulsesto the plurality of electrodes at a rate of between 10 Hz and 5 MHz;where the pulse-generation system is configured to apply the voltagepulses to the plurality of electrodes such that portions of the liquidare vaporized to propagate shockwaves through the liquid and theshockwave outlet.

Some embodiments of the present apparatuses (for generating therapeuticshock waves) comprise: a housing defining a chamber and a shockwaveoutlet, the chamber configured to be filled with a liquid; and aplurality of electrodes disposed in the chamber to define a plurality ofspark gaps; where the plurality of electrodes is configured to receivevoltage pulses from a pulse-generation system at a rate of between 10 Hzand 5 MHz such that portions of the liquid are vaporized to propagateshockwaves through the liquid and the shockwave outlet.

Some embodiments of the present apparatuses (for generating therapeuticshock waves) comprise: a housing defining a chamber and a shockwaveoutlet, the chamber configured to be filled with a liquid; and aplurality of electrodes configured to be disposed in the chamber todefine one or more spark gaps; where the plurality of electrodes isconfigured to receive voltage pulses from a pulse-generation system suchthat portions of the liquid are vaporized to propagate shockwavesthrough the liquid and the shockwave outlet; and where the housingcomprises a translucent or transparent window that is configured topermit a user to view a region of a patient comprising target cells.

In some embodiments of the present apparatuses, the plurality ofelectrodes are not visible to a user viewing a region through the windowand the shockwave outlet. Some embodiments further comprise: an opticalshield disposed between the window and the plurality of electrodes. Insome embodiments, the plurality of electrodes are offset from an opticalpath extending through the window and the shockwave outlet. Someembodiments further comprise: an acoustic mirror configured to reflectshockwaves from the plurality of electrodes to the shockwave outlet. Insome embodiments, the acoustic mirror comprises glass. In someembodiments, the one or more spark gaps comprise a plurality of sparkgaps. In some embodiments, the plurality of electrodes are configured tobe removably coupled to the pulse-generation system. In someembodiments, the housing is replaceable.

Some embodiments of the present apparatuses further comprise: a sparkmodule comprising: a sidewall configured to releasably couple the sparkmodule to the housing; where the plurality of electrodes is coupled tothe sidewall such that the plurality of electrodes is disposed in thechamber if the spark module is coupled to the housing. In someembodiments, the sidewall comprises a polymer. In some embodiments, thesidewall of the spark module is configured to cooperate with the housingto define the chamber. In some embodiments, the sidewall defines a sparkchamber within which the plurality of electrodes is disposed, the sparkchamber is configured to be filled with a liquid, and at least a portionof the sidewall is configured to transmit shockwaves from a liquid inthe spark chamber to a liquid in the chamber of the housing. In someembodiments, the sidewall of the spark module comprises at least one ofpins, grooves, or threads, and the housing comprises at least one ofcorresponding grooves, pins, or threads to releasably couple the sparkmodule to the housing. In some embodiments, the housing includes a firstliquid connector configured to fluidly communicate with the chamber whenthe spark module is coupled to the housing, and the sidewall of thespark module includes a second liquid connector configured to fluidlycommunicate with the chamber when the spark module is coupled to thehousing In some embodiments of the present apparatuses, the housingfurther comprises two liquid connectors. Some embodiments furthercomprise: a liquid reservoir; and a pump configured to circulate liquidfrom the reservoir to the chamber of the housing via the two liquidconnectors.

In some embodiments of the present apparatuses, the pulse-generationsystem is configured to apply voltage pulses to the plurality ofelectrodes at a rate of between 20 Hz and 200 Hz. In some embodiments,the pulse-generation system is configured to apply voltage pulses to theplurality of electrodes at a rate of between 50 Hz and 200 Hz. In someembodiments, the pulse-generation system comprises: a firstcapacitive/inductive coil circuit comprising: an induction coilconfigured to be discharged to apply at least some of the voltagepulses; a switch; and a capacitor; where the capacitor and the switchare coupled in parallel between the induction coil and a current source.In some embodiments, the pulse-generation system comprises: a secondcapacitive/inductive coil circuit similar to the firstcapacitive/inductive coil circuit; and a timing unit configured tocoordinate the discharge of the induction coils of each of the first andsecond capacitive/inductive coil circuits.

Some embodiments of the present apparatuses comprise: a spark modulethat comprises: a sidewall configured to releasably couple the sparkmodule to a probe; a plurality of electrodes disposed on a first side ofthe sidewall and defining one or more spark gaps; and a plurality ofelectrical connectors in electrical communication with the plurality ofelectrodes and configured to releasably connect the electrodes to apulse-generation system to generate sparks across the one or more sparkgaps. In some embodiments, the sidewall comprises a polymer. In someembodiments, the sidewall includes a liquid connector configured tocommunicate liquid through the sidewall In some embodiments, thesidewall defines a spark chamber within which the plurality ofelectrodes is disposed, the spark chamber is configured to be filledwith a liquid, and at least a portion of the sidewall is configured totransmit shockwaves from a liquid in the spark chamber to a liquid inthe chamber of the housing. In some embodiments, the spark modulefurther comprises one or more liquid connectors in fluid communicationwith the spark chamber such that the spark chamber can be filled with aliquid. In some embodiments, the one or more liquid connectors comprisetwo liquid connectors through which a liquid can be circulated throughthe spark chamber. In some embodiments, the sidewall is configured toreleasably couple the spark module to a probe having a chamber such thatthe electrodes are disposed within the chamber of the probe. In someembodiments, the sidewall and the probe cooperate to define the chamber.In some embodiments, the spark module further comprises one or moreliquid connectors in fluid communication with the chamber of the probesuch that the chamber of the probe can be filled with a liquid throughthe one or more liquid connectors. In some embodiments, the one or moreliquid connectors comprise two liquid connectors through which a liquidcan be circulated through the chamber of the probe via the two liquidconnectors. In some embodiments, the spark module includes a firstliquid connector configured to fluidly communicate with the chamber whenthe spark module is coupled to the probe and the probe includes a secondliquid connector configured to fluidly communicate with the chamber whenthe spark module is coupled to the probe.

In some embodiments of the present apparatuses comprising a sparkmodule, the one or more spark gaps comprise a plurality of spark gaps.In some embodiments, the plurality of electrodes comprises three or fourelectrodes defining two spark gaps. In some embodiments, the three orfour electrodes comprises a first peripheral electrode, a secondperipheral electrode spaced apart from the first electrode, and one ortwo central electrodes configured to move back and forth between theperipheral electrodes. In some embodiments, the spark module furthercomprises: an elongated member coupled to the one or two centralelectrodes and configured to move to carry the one or two centralelectrodes back and forth between the peripheral electrodes. In someembodiments, the one or two central electrodes comprise two centralelectrodes in electrical communication with each other and disposed onopposing sides of the elongated member. In some embodiments, theelongated member is configured to self-adjust the spark gap between theperipheral electrodes and the one or two central electrodes within anexpected range of operating frequencies. In some embodiments, theexpected range of operating frequencies is between 10 Hz and 5 MHz. Insome embodiments, the elongated member is pivotally coupled to thesidewall and biased toward an initial position by one or more springarms. In some embodiments, the elongated member and the one or morespring arms are configured to determine a pulse rate of the spark modulewithin an expected range of operating frequencies. In some embodiments,the expected range of operating frequencies is between 10 Hz and 5 MHz.In some embodiments, the apparatus is configured to discharge electricalpulses between the electrodes while the electrodes are submerged in aliquid such that movement of the elongated member automatically andalternatingly adjusts the spark gap between the one or two centralelectrodes and each of the peripheral electrodes. In some embodiments,the elongated member comprises a resilient beam having a base that iscoupled in fixed relation to the sidewall. In some embodiments, theresilient beam is configured to determine a pulse rate of the sparkmodule at expected operating conditions. In some embodiments, theapparatus is configured to discharge electrical pulses between theelectrodes while the electrodes are submerged in a liquid such thatmovement of the resilient beam automatically and alternatingly adjuststhe spark gap between the one or two central electrodes and each of theperipheral electrodes.

In some embodiments of the present apparatuses comprising a sparkmodule, the sidewall of the spark module comprises at least one of pins,grooves, or threads, and is configured to be coupled to a probe thatcomprises at least one of corresponding grooves, pins, or threads toreleasably couple the spark module to the housing. Some embodimentsfurther comprise: a probe configured to be coupled to the spark modulesuch that the plurality of electrodes is disposed in a chamber that isfillable with a liquid, and such that shockwaves originating at theelectrodes will travel through a shockwave outlet of the apparatus. Insome embodiments, the chamber is filled with liquid. In someembodiments, the probe does not define an additional chamber, such thatthe spark chamber is the only chamber through which shockwavesoriginating at the electrodes will propagate. In some embodiments, theprobe defines a second chamber within which the spark chamber isdisposed if the spark module is coupled to the probe. In someembodiments, the probe includes a plurality of electrical connectorsconfigured to be coupled to the plurality of electrical connectors ofthe spark module. In some embodiments, the probe includes one or moreliquid connectors configured to be coupled to the one or more liquidconnectors of the spark module. In some embodiments, the probe includestwo liquid connectors configured to be coupled to the two liquidconnectors of the spark module. In some embodiments, the spark module isconfigured to be coupled to the probe such that the electrical andliquid connectors of the spark module are simultaneously connected tothe respective electrical and liquid connectors of the probe as thespark module is coupled to the probe. In some embodiments, the probeincludes one or more liquid connectors configured to be coupled to theone or more liquid connectors of the spark module. In some embodiments,the probe includes a combined connection having two or more electricalconductors and two lumens for communicating liquid, the combinedconnection configured to be coupled to a combined tether or cable thathas two or more electrical conductors and two lumens for communicatingliquid. In some embodiments, combined connection is configured to beremovably coupled to the combined tether or cable.

In some embodiments of the present apparatuses comprising a spark moduleand a probe, the probe includes a housing with a translucent ortransparent window that is configured to permit a user to view a regionof a patient comprising target cells. In some embodiments, if the sparkmodule is coupled to the probe, the plurality of electrodes is notvisible to a user viewing a region through the window and the shockwaveoutlet. Some embodiments further comprise: an optical shield disposedbetween the window and the plurality of electrodes. In some embodiments,the optical shield includes a light-sensitive material that darkens orincreases in opacity in the presence of bright light. In someembodiments, the plurality of electrodes are offset from an optical pathextending through the window and the shockwave outlet. Some embodimentsfurther comprise: an acoustic mirror configured to reflect shockwavesfrom the plurality of electrodes to the shockwave outlet. In someembodiments, the acoustic mirror comprises glass.

Some embodiments of the present apparatuses comprise: a probe configuredto be coupled to a spark module having a plurality of electrodesdefining one or more spark gaps such that the plurality of electrodes isdisposed in a chamber that is fillable with a liquid. In someembodiments, the chamber is filled with liquid. In some embodiments, theprobe is configured to cooperate with the spark module to define thechamber. In some embodiments, the probe includes a first liquidconnector configured to fluidly communicate with the chamber when thespark module is coupled to the probe, and is configured to be coupled toa spark module that includes a second liquid connector that isconfigured to fluidly communicate with the chamber when the spark moduleis coupled to the probe.

In some embodiments, the spark module includes a sidewall defining aspark chamber within which the plurality of electrodes are disposed, andthe probe does not define an additional chamber, such that the sparkchamber is the only chamber through which shockwaves originating at theelectrodes will propagate. In some embodiments, the spark moduleincludes a sidewall defining a spark chamber within which the pluralityof electrodes are disposed, where the probe defines a second chamberwithin which the spark chamber is disposed if the spark module iscoupled to the probe. In some embodiments, the probe includes aplurality of electrical connectors configured to be coupled to aplurality of electrical connectors of the spark module that are inelectrical communication with the plurality of electrodes. In someembodiments, the probe includes one or more liquid connectors configuredto be coupled to one or more liquid connectors of the spark module. Insome embodiments, the probe includes two liquid connectors configured tobe coupled to the two liquid connectors of the spark module. In someembodiments, the spark module is configured to be coupled to the probesuch that the electrical and liquid connectors of the spark module aresimultaneously connected to the respective electrical and liquidconnectors of the probe as the spark module is coupled to the probe.

In some embodiments of the present apparatuses comprising a probe, theprobe includes a combined connection having two or more electricalconductors and two lumens for communicating liquid, the combinedconnection configured to be coupled to a combined tether or cable thathas two or more electrical conductors and two lumens for communicatingliquid. In some embodiments, the combined connection is configured to beremovably coupled to the combined tether or cable. In some embodiments,the probe includes a housing with a translucent or transparent windowthat is configured to permit a user to view a region of a patientcomprising target cells. In some embodiments, if the spark module iscoupled to the probe, the plurality of electrodes is not visible to auser viewing a region through the window and the shockwave outlet. Someembodiments further comprise: an optical shield disposed between thewindow and the plurality of electrodes. In some embodiments, theplurality of electrodes are offset from an optical path extendingthrough the window and the shockwave outlet. Some embodiments furthercomprise: an acoustic mirror configured to reflect shockwaves from theplurality of electrodes to the shockwave outlet. In some embodiments,the acoustic mirror comprises glass.

Some embodiments of the present apparatuses comprising a probe furthercomprise: a pulse-generation system configured to repeatedly store andrelease an electric charge, the pulse-generation system configured to becoupled to the electrical connectors of the spark module to release theelectric charge through the electrodes of the spark module. In someembodiments, the pulse-generation system is configured to apply voltagepulses to the plurality of electrodes at a rate of between 20 Hz and 200Hz. In some embodiments, the pulse-generation system is configured toapply voltage pulses to the plurality of electrodes at a rate of between50 Hz and 200 Hz. In some embodiments, the pulse-generation systemincludes a single charge/discharge circuit. In some embodiments, thepulse-generation system includes a plurality of charge/dischargecircuits and a timing unit configured to coordinate charging anddischarging of the plurality of charge/discharge circuits. In someembodiments, each of the charge/discharge circuits includes acapacitive/inductive coil circuit. In some embodiments, eachcapacitive/inductive coil circuit comprises: an induction coilconfigured to be discharged to apply at least some of the voltagepulses; a switch; and a capacitor; where the capacitor and the switchare coupled in parallel between the induction coil and the timing unit.Some embodiments further comprise: a liquid reservoir; and a pumpconfigured to circulate liquid from the reservoir to the chamber of thehousing.

Some embodiments of the present apparatuses comprise: a pulse-generationsystem including a plurality of charge/discharge circuits and a timingunit configured to coordinate charging and discharging of the pluralityof charge/discharge circuits at a rate of between 10 where thepulse-generation system is configured to be coupled to a plurality ofelectrodes of a spark module to discharge the charge/discharge circuitsthrough the electrodes. Some embodiments further comprise: configuredeach of the charge/discharge circuits includes a capacitive/inductivecoil circuit. each capacitive/inductive coil circuit comprises: aninduction coil configured to be discharged to apply at least some of thevoltage pulses; a switch; and a capacitor; where the capacitor and theswitch are coupled in parallel between the induction coil and the timingunit. the pulse-generation system is configured to apply voltage pulsesto the plurality of electrodes at a rate of between 20 Hz and 200 Hz.the pulse-generation system is configured to apply voltage pulses to theplurality of electrodes at a rate of between 50 Hz and 200 Hz. Someembodiments further comprise: a liquid reservoir; and a pump configuredto circulate liquid from the reservoir to the chamber of the housing.

Some embodiments of the present methods comprise: positioning theshockwave outlet of one of the present apparatuses adjacent to a regionof a patient comprising target cells; and activating a pulse-generationsystem to propagate a shockwaves through the fluid to the target cells.In some embodiments, at least a portion of the plurality of shock wavesare delivered to a portion of an epidermis layer of a patient thatincludes a tattoo. In some embodiments, a housing and/or probe of theapparatus includes a translucent or transparent window that isconfigured to permit a user to view a region of a patient comprisingtarget cells; and the method further comprises: viewing the regionthrough the window while positioning the apparatus. In some embodiments,the apparatus includes a spark module (that comprises: a sidewallconfigured to releasably couple the spark module to the housing; wherethe plurality of electrodes is coupled to the sidewall such that theplurality of electrodes is disposed in the chamber if the spark moduleis coupled to the housing), and the method further comprises: couplingthe spark module to the housing prior to activating the pulse-generationsystem.

Some embodiments of the present methods comprise: electro-hydraulicallygenerating a plurality of shock waves at a frequency of between 10;delivering at least a portion of the plurality of shock waves to atleast one cellular structure comprising at least one region ofheterogeneity; and rupturing the at least one cellular structure withthe continued delivery of the plurality of shock waves. In someembodiments, the at least one region of heterogeneity comprises aneffective density greater than an effective density of the at least onecellular structure. Some embodiments further comprise the step ofvarying the frequency of the acoustic waves. In some embodiments, atleast a portion of the plurality of shock waves are delivered to anepidermis layer of a patient. In some embodiments, a portion of theepidermis layer receiving the shock waves includes cells that containtattoo pigment particles. Some embodiments further comprise: identifyingat least one target cellular structure be ruptured prior to deliveringat least a portion of shock waves to the at least one target cellularstructure.

Some embodiments of the present methods comprise: delivering a pluralityof electro-hydraulically generated shock waves to at least one cellularstructure comprising at least one region of heterogeneity until the atleast one cellular structure ruptures. In some embodiments, at least aportion of the plurality of shock waves are delivered to a portion of anepidermis layer of a patient that includes cells that contain tattoopigment particles. In some embodiments, the shock waves are delivered tothe at least one cellular structure for no more than 30 minutes in a24-hour period. In some embodiments, the shock waves are delivered tothe at least one cellular structure for no more than 20 minutes in a24-hour period. In some embodiments, between 200 and 5000 shockwaves aredelivered in between 30 seconds and 20 minutes at each of a plurality ofpositions of a shockwave outlet. Some embodiments further comprise:tensioning a portion of a patient's skin while delivering theshockwaves. In some embodiments, the tensioning is performed by pressinga convex outlet member against the portion of the patient's skin. Someembodiments further comprise: delivering laser light to the at least onecellular structure; and/or delivering a chemical or biological agent tothe at least one cellular.

Any embodiment of any of the present systems, apparatuses, and methodscan consist of or consist essentially of—rather thancomprise/include/contain/have—any of the described steps, elements,and/or features. Thus, in any of the claims, the term “consisting of” or“consisting essentially of” can be substituted for any of the open-endedlinking verbs recited above, in order to change the scope of a givenclaim from what it would otherwise be using the open-ended linking verb.

Details associated with the embodiments described above and others arepresented below.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings illustrate by way of example and not limitation.For the sake of brevity and clarity, every feature of a given structureis not always labeled in every figure in which that structure appears.Identical reference numbers do not necessarily indicate an identicalstructure. Rather, the same reference number may be used to indicate asimilar feature or a feature with similar functionality, as maynon-identical reference numbers. The figures are drawn to scale (unlessotherwise noted), meaning the sizes of the depicted elements areaccurate relative to each other for at least the embodiment depicted inthe figures.

FIG. 1 depicts a block diagram of a first embodiment of the presentelectro-hydraulic (EH) shockwave generating systems.

FIG. 2 depicts a cross-sectional side view of a handheld probe for someembodiments of the present EH shockwave generating systems.

FIG. 2A depicts a cross-sectional side view of a first embodiment of aremovable spark head usable with embodiments of the present handheldprobes, such as the one of FIG. 2.

FIG. 2B depicts a cutaway side view of a second embodiment of aremovable spark head usable with embodiments of the present handheldprobes, such as the one of FIG. 2.

FIG. 2C depicts a cutaway side view of a third embodiment of a removablespark head usable with embodiments of the present handheld probes, suchas the one of FIG. 2.

FIG. 3A-3B depict a timing diagrams of one example of the timedapplication of energy cycles or voltage pulses in the system of FIG. 1and/or the handheld probe of FIG. 2.

FIG. 4 depicts a waveform that can be emitted by system of FIG. 1 and/orthe handheld probe of FIG. 2 into target tissue.

FIG. 5 depicts a schematic diagram of one embodiment of a multi-gappulse-generation system for use in or with some embodiments of thepresent systems.

FIG. 6 depicts a block diagram of an embodiment of a radio-frequency(RF) powered acoustic ablation system.

FIGS. 7A-7B depict perspective and cross-sectional views of a firstprototyped spark chamber housing.

FIG. 8 depicts a cross-sectional view of a second prototyped embodimentof spark chamber housing.

FIG. 9 depicts a schematic diagram of an electric circuit for aprototyped pulse-generation system.

FIG. 10 depicts a conceptual flowchart of one embodiment of the presentmethods.

FIG. 11 depicts an exploded perspective view of a further prototypedembodiment of the present probes having a spark head or module.

FIGS. 12A and 12B depict parts of the assembly of the probe of FIG. 11.

FIGS. 13A and 13B depict perspective and side cross-sectional views,respectively, of the probe of FIG. 11.

FIG. 13C depicts an enlarged side cross-sectional view of a spark gap ofthe probe of FIG. 11.

FIG. 14 depicts a schematic diagram of a second embodiment of anelectric circuit for a prototyped pulse-generation system.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The term “coupled” is defined as connected, although not necessarilydirectly, and not necessarily mechanically; two items that are “coupled”may be unitary with each other. The terms “a” and “an” are defined asone or more unless this disclosure explicitly requires otherwise. Theterm “substantially” is defined as largely but not necessarily whollywhat is specified (and includes what is specified; e.g., substantially90 degrees includes 90 degrees and substantially parallel includesparallel), as understood by a person of ordinary skill in the art. Inany disclosed embodiment, the terms “substantially,” “approximately,”and “about” may be substituted with “within [a percentage] of” what isspecified, where the percentage includes 0.1, 1, 5, and 10 percent.

The terms “comprise” (and any form of comprise, such as “comprises” and“comprising”), “have” (and any form of have, such as “has” and“having”), “include” (and any form of include, such as “includes” and“including”) and “contain” (and any form of contain, such as “contains”and “containing”) are open-ended linking verbs. As a result, a system orapparatus that “comprises,” “has,” “includes” or “contains” one or moreelements possesses those one or more elements, but is not limited topossessing only those elements. Likewise, a method that “comprises,”“has,” “includes” or “contains” one or more steps possesses those one ormore steps, but is not limited to possessing only those one or moresteps.

Further, a structure (e.g., a component of an apparatus) that isconfigured in a certain way is configured in at least that way, but itcan also be configured in other ways than those specifically described.

Certain embodiments of the present systems and apparatuses areconfigured to generate high-frequency shock waves in a predictable andconsistent manner. In some embodiments, the generated EH shock waves canbe used in medical and/or aesthetic therapeutic applications (e.g., whendirected at and/or delivered to target tissue of a patient). Examples ofmedical and/or aesthetic therapeutic applications in which the presentsystems can be used are disclosed in: (1) U.S. patent application Ser.No. 13/574,228, published as US 2013/0046207; and (2) U.S. patentapplication Ser. No. 13/547,995, published as, published as US2013/0018287; both of which are incorporated here in their entireties.The EH shock waves generated by the present systems can be configured toimpose sufficient mechanical stress to rupture in cells of the targettissue (e.g., through membrane-degradation damage).

When targeted cells (cells of target tissue) are exposed to thegenerated high-PR shockwaves, the cells experience sharp gradients ofmechanical stress due to the spatial heterogeneity parameters of thecells, such as density and shear elasticity modulus of the differentcomponents of the cell. For instance, dense and/or inelastic componentsinside a cell undergo greater mechanical stress when subjected to shockwaves as compared to lighter components. In particular, acceleration ofhigher-density particles or components within the cellular structureexposed to the impact front is typically very large. At the same time,the impact on lower-density biological structures making up the cellstructure when exposed to such a large gradient of pressure issignificantly reduced because the elasticity of the lower-densitybiological structures allows them to generally act as low-compliancematerial. The difference in mechanical stress results in movement of thedense and/or inelastic components within the cell.

When the cell is exposed to repeated shock waves at a certain frequencyand energy level, the dense and/or inelastic components are repeatedlymoved until they break out of the cell, thereby rupturing the cell. Inparticular, the properties mismatch of the cellular structure and cells'ability to experience deformation when exposed to the impact front leadto cellular destruction as described. One possible theory to explain thephenomenon of rupturing cellular structure can be found in (Burov, V.A., 2002) [1], which is incorporated herein by reference in itsentirety.

As discussed by Burov [1], while a cell may oscillate as an integralunit when impacted by these pressure fronts, sharp gradients ofmechanical stress can be generated inside the cell as a result ofspatial heterogeneity parameters (i.e., density and shear elasticitymodulus). This concept can be illustrated by modeling the biologicalstructure as two linked balls with masses m₁ and m₂ and the density (ρ₀)of the liquid oscillating around the balls with the speed μ_(o)(t)differ insignificantly from the densities of the balls (by ρ₁ and ρ₂respectively). If only the resistance to potential flow is taken intoaccount, the force applied to the link is calculated as shown inEquation (1):

$\begin{matrix}{F = {\frac{2}{3}\frac{m_{1}m_{2}}{m_{1} + m_{2}}\frac{\left\lbrack {\rho_{1} - \rho_{2}} \right\rbrack}{\rho_{0}}{\mu_{0}(t)}}} & (1)\end{matrix}$

Additional discussions of Equation (1) and its variables are furtherprovided in [1]. For example, if the ball radius (R) is about 10 μm andthe difference between the densities of the balls is 0.1 ρ₀, and resultsin a stress force, F/(πR²)m of 10⁹ dyne/cm². This is sufficient torupture a cell membrane. The embodiments of the present apparatusesgenerate shock waves in a controlled manner that can be used to causetargeted damage to certain cells, which have medical and/or aesthetictherapeutic applications that are discussed further below.

Another possible theory to explain the phenomenon of cell rupturing isthe accumulation shear stress in the denser material in the cellularstructure. In heterogeneous media, such as cells with particles (e.g.,pigment particles), shock waves cause the cell membranes to fail by aprogressive (i.e., accumulated) shearing mechanism. On the other hand,in homogeneous media, compression by shock waves causes minimal, if any,damage to membranes. Microscopic focusing and defocusing of the shockwave as it passes through the heterogeneous media can result in shockwave strengthening or weakening locally that result in an increase inlocal shearing. Relative shearing motion of the cell membrane occurs onthe scale of the heterogeneities of the cellular structure. It isbelieved that when shock waves strike a region of heterogeneities (e.g.,cells containing particles), the particle motion that is out of phasewith the incoming waves generates cell disruptive energy transfer (e.g.,shear stress). The out of phase motion (e.g., shear stress) causesmicroscopic damage to the cell membrane that can progressively grow intocell membrane failure with additional successive accumulation of shearstress.

The progressive shearing mechanism of repeated exposure to shock wavescan be considered dynamic fatigue of the cell membranes. Damage fromdynamic fatigue is dependent on three factors: (1) applied stress orstrain, (2) the rate at which the strain is applied, and (3) accumulatednumber of strain cycles. These three factors can be manipulated to causea cell with heterogeneities to experience catastrophic cell membranefailure as compared to a relatively more homogeneities at a particularapplied strain, strain rate, and strain cycles.

The manipulation of the factors can be done by providing EH shock wavesof certain properties, such as the number of shock waves, the amount oftime between each shock wave, and the strength of the applied shockwaves. As discussed above, if there is too much time between shock wavesfor the tissue to relax to its unstrained state, the cells will becomemore resistant to failure. As such, in the preferred embodiment for anEH system, shock waves at a PR greater than 5 Hz and preferably greaterthan 100 Hz and most preferably greater than 1 MHz are delivered to thetargeted cellular structures to achieve dynamic fatigue of the tissueand not allow the tissue time to relax.

At high enough PR, tissues behave as a viscous material. As a result,the PR and power level can be adjusted to account for the tissue'sviscous properties.

A third possible theory is that the EH shock waves cause a combinationof effects of direct movement of the particles contained in the cellularstructure and dynamic fatigue that rupture the cells. Whileparticle-containing cells are an apparent example of cellular structuresexhibiting heterogeneities, their description is not intended to limitthe scope of the present disclosure. Instead, the embodiments disclosedherein can be used to rupture or cause damage to other cellularstructures that exhibit heterogeneities, such as cellular structuresthat have different effective density regions. The parameters of theshock waves generated according to the disclosed aspects can be adjustedbased, at least, on the regions of different effective densities (i.e.heterogeneities) to cause cellular damage as described herein.Heterogeneities can be regions within a single cell, a region ofdifferent types of cells, or a combination of both. In certainembodiments, a region of heterogeneity within a cell includes a regionhaving an effective density greater than the effective density of thecell. In one specific example, the effective density of a fibroblastcell is about 1.09 g/cm³, a region of heterogeneity in the cell would beparticles contained within the cell that have an effective densitygreater than 1.09 g/cm², such as graphite with a density of 2.25 g/cm³.In certain embodiments, a region of cellular heterogeneity between cellsincludes a region with different types of cells, where each cell typehas a different effective density, such as fibroblast cells and fatcells or hair follicles. The present disclosure provides furtherexamples of cellular structures containing heterogeneities below.

Referring now to the drawings, and more particularly to FIG. 1, showntherein and designated by the reference numeral 10 is a block diagram ofone embodiment of the present apparatuses or systems forelectro-hydraulically generating shockwaves in a controlled manner. Insome embodiments, such as the one shown, system 10 includes a handheldprobe (e.g., with a first housing, such as in FIG. 2) and a separatecontroller or pulse-generation system (e.g., in or with a second housingcoupled to the handheld probe via a flexible cable or the like). Inother embodiments, the present systems include a single handheldapparatus disposed in a single housing.

In the embodiment shown, apparatus 10 comprises: a housing 14 defining achamber 18 and a shockwave outlet 20; a liquid (54) disposed in chamber18; a plurality of electrodes (e.g., in spark head or module 22)configured to be disposed in the chamber to define one or more sparkgaps; and a pulse-generation system 26 configured to apply voltagepulses to the electrodes at a rate of between 10 Hz and 5 MHz. In thisembodiment, the capacitive/inductive coil system 26 is configured toapply the voltage pulses to the electrodes such that portions of theliquid are vaporized to propagate shockwaves through the liquid and theshockwave outlet.

In the embodiment shown, pulse-generation system 26 is configured foruse with an alternating current power source (e.g., a wall plug). Forexample, in this embodiment, pulse-generation system 26 comprises a plug30 configured to be inserted into a 110V wall plug. In the embodimentshown, pulse-generation system 26 comprises a capacitive/inductive coilsystem, on example of which is described below with reference to FIG. 6.In other embodiment, pulse-generation system 26 can comprise anysuitable structure or components configured to apply high voltages tothe electrodes in a periodic fashion to generate electric sparks ofsufficient power to vaporize liquid in the respective spark gaps, asdescribed in this disclosure.

In the embodiment shown, pulse-generation system 26 is (e.g., removably)coupled to the electrodes in spark head or module 22 via a high-voltagecable 34, which may, for example, include two or more electricalconductors and/or be heavily shielded with rubber or other type ofelectrically insulating material to prevent shock. In some embodiments,high-voltage cable 34 is a combined tether or cable that furtherincludes one or more (e.g., two) liquid lumens through which chamber 18can be filled with liquid and/or via which liquid can be circulatedthrough chamber 18 (e.g., via combined connection 36). In the embodimentshown, apparatus 10 comprises a handheld probe or handpiece 38 and cable34 is removably coupled to probe 38 via a high-voltage connector 42,which is coupled to spark head or module 22 via two or more electricalconductors 44. In the embodiment shown, probe 38 comprises a head 46 anda handle 50, and probe 38 can comprise a polymer or other electricallyinsulating material to enable an operator to grasp handle 50 to positionprobe 38 during operation. For example, handle 50 can be molded withplastic and/or can be coated with an electrically insulating materialsuch as rubber.

In the embodiment shown, a liquid 54 (e.g., a dielectric liquid such asdistilled water) is disposed in (e.g., and substantially fills) chamber18. In this embodiment, spark head 22 is positioned in chamber 18 andsurrounded by the liquid such that the electrodes can receive voltagepulses from pulse-generation system 26 (e.g., at a rate of between 10 Hzand 5 MHz) such that portions of the liquid are vaporized to propagateshockwaves through the liquid and shockwave outlet 20. In the embodimentshown, probe 38 includes an acoustic delay chamber 58 between chamber 18and outlet 20. In this embodiment, acoustic delay chamber issubstantially filled with a liquid 62 (e.g., of the same type as liquid54) and has a length 66 that is sufficient to permit shockwaves to formand/or be directed toward outlet 20. In some embodiments, length 66 maybe between 2 millimeters (mm) and 25 millimeters (mm). In the embodimentshown, chamber 18 and acoustic-delay chamber 58 are separated by a layerof sonolucent (acoustically permeable or transmissive) material thatpermits sound waves and/or shockwaves to travel from chamber 18 intoacoustic-delay chamber 58. In other embodiments, liquid 62 may bedifferent than liquid 54 (e.g., liquid 62 may comprise bubbles, water,oil, mineral oil, and/or the like). Certain features such as bubbles mayintroduce and/or improve a nonlinearity in the acoustic behavior ofliquid 54 to increase the formation of shockwaves. In furtherembodiments, chamber 18 and acoustic-delay chamber 54 may be unitary(i.e., may comprise a single chamber). In further embodiments,acoustic-delay chamber 54 may be replaced with a solid member (e.g., asolid cylinder of elastomeric material such as polyurethane). In theembodiment shown, probe 38 further includes an outlet member 70removably coupled to the housing at a distal end of the acoustic delaychamber, as shown. Member 70 is configured to contact tissue 74, and canbe removed and either sterilized or replaced between patients. Member 70comprises a polymer or other material (e.g., low-density polyethylene orsilicone rubber) that is acoustically permeable to permit shockwaves toexit acoustic-delay chamber 58 via outlet 20. Tissue 74 may, forexample, be human skin tissue to be treated with apparatus 10, and may,for example, include a tattoo, a blemish, a subdermal lesion, or a basalcell abnormality. In some embodiments, an acoustic coupling gel (notshown) may be disposed between member 70 and tissue 74 to lubricate andprovide additional acoustic transmission into tissue 74.

In the embodiment shown, probe 38 includes an acoustic mirror 78 thatcomprises a material (e.g., glass) and is configured to reflect amajority of sound waves and/or shock waves that are incident on theacoustic mirror. As shown, acoustic mirror 58 can be angled to reflectsound waves and/or shockwaves (e.g., that originate at spark head 22)toward outlet 20 (via acoustic-delay chamber). In the embodiment shown,housing 14 can comprise a translucent or transparent window 82 that isconfigured to permit a user to view (through window 82, chamber 18,chamber 58, and member 70) a region of a patient (e.g., tissue 74)comprising target cells (e.g., during application of shockwaves or priorto application of shockwaves to position outlet 20 at the targettissue). In the embodiment shown, window 82 comprises an acousticallyreflective material (e.g., glass) that is configured to reflect amajority of sound waves and/or shock waves that are incident on thewindow. For example, window 82 can comprise clear glass of sufficientthickness and strength to withstand the high-energy acoustic pulsesproduced at spark head 22 (e.g., tempered plate glass having a thicknessof about 2 mm and an optical transmission efficiency of greater than50%).

In FIG. 1, a human eye 86 indicates a user viewing the target tissuethrough window 82, but it should be understood that target tissue may be“viewed” through window 82 via a camera (e.g., a digital still and/orvideo camera). By direct or indirect observation, acoustic energy can bepositioned, applied, and repositioned according to target tissues, suchas extant tattoos, and by indications of acoustic energy, such as achange in the color of the tissue. However, if spark head 22 is disposedwhere a user can view spark head 22, the brightness of the resultingspark from spark head 22 may be too bright for a user to comfortablyview, and in the embodiment shown, probe 38 is configured such that theplurality of electrodes are not visible to a user viewing a region(e.g., of target tissue) through window 82 and outlet 20. For example,in the embodiment shown, probe 38 includes an optical shield 90 disposedbetween spark head 22 and window 82. Shield 90, for example, can have awidth and/or a length that are less than a corresponding width and/orlength of window 82 such that shield 90 is large enough to substantiallyblock light from spark head 22 from traveling directly to the user'seye, but does not interfere with the field-of-view through window 82 andoutlet 20 more than is necessary to block that light. Shield 90 can, forexample, comprise a thin sheet of metal, such as stainless steel, orother opaque material, or can comprise welder's glass (e.g., an LCDdarkened by a photocell or other light-sensitive material) that isoptically activated and darkened by the brightness of sparks at thespark gaps. The acoustic effect of shielding the resulting sparks from aspark gap head must be considered in order to maintain the effect of apoint source from spark head 22 and a resulting desired planarwavefront. If shield 90 comprises an acoustically reflective material,to prevent pulse broadening, the distance between the shield and thespark gaps between electrodes in spark head 22 may be selected tominimize (e.g., at least destructive) interference between sound wavesand/or shockwaves reflected from the shield and sound waves and/orshockwaves originating at spark head 22 (e.g., such that intersectingwaves do not produce excess echoes or reverberation). With a velocity ofsound waves in a medium such as distilled water of about 1500 m/Sec, thedistance between the spark head and the shield may be calculated to beat ½ and ¾ wavelengths from the source.

Spark head 22 (e.g., the electrodes in spark head 22) may have a limitedlifetime that may be extended by limiting the duration of activation. Inthe embodiment shown, apparatus 10 includes a switch or trigger 94coupled to pulse-generation system 26 via a switch wire or otherconnection 98 through connector 42, such that switch 94 can be actuatedto apply voltage pulses to the electrodes in spark head 22.

FIG. 2 depicts a cross-sectional side view of a second embodiment 38 aof the present handheld probes or handpiece for use with someembodiments of the present EH shockwave generating systems andapparatuses. Probe 38 a is substantially similar in some respects toprobe 38, and the differences are therefore primarily described here.For example, probe 38 a is also configured such that the plurality ofelectrodes of spark head or module 22 a are not visible to a userviewing a region (e.g., of target tissue) through window 82 a and outlet20 a. However, rather than including an optical shield, probe 38 a isconfigured such that spark head 22 a (and the electrodes of the sparkhead) are offset from an optical path extending through window 82 a andoutlet 20 a. In this embodiment, acoustic mirror 78 a is positionedbetween spark head 22 a and outlet 20 a, as shown, to define a boundaryof chamber 18 a and to direct acoustic waves and/or shockwaves fromspark head 22 a to outlet 20 a. In the embodiment shown, window 82 a cancomprise a polymer or other acoustically permeable or transmissivematerial because acoustic mirror 78 a is disposed between window 82 aand chamber 18 a and sound waves and/or shockwaves are not directlyincident on window 82 a (i.e., because the sound waves and/or shockwaves are primarily reflected by acoustic mirror 78 a).

In the embodiment shown, spark head 22 a includes a plurality ofelectrodes 100 that define a plurality of spark gaps. The use ofmultiple spark gaps can be advantageous because it can double the numberof pulses that can be delivered in a given period of time. For example,after a pulse vaporizes an amount of liquid in a spark gap the vapormust either return to its liquid state or must be displaced by adifferent portion of the liquid that is still in a liquid state. Inaddition to the time required for the spark gap to be re-filled withwater before a subsequent pulse can vaporize additional liquid, sparksalso heat the electrodes. As such, for a given spark rate, increasingthe number of spark gaps reduces the rate at which each spark gap mustbe fired and thereby extends the life of the electrodes. Thus, ten sparkgaps potentially increases the possible pulse rate and/or electrode lifeby a factor of ten.

As noted above, high pulse rates can generate large amounts of heat thatmay increase fatigue on the electrodes and/or increase the timenecessary for vapor to return to the liquid state after it is vaporized.In some embodiments, this heat can be managed by circulating liquidaround the spark head. For example, in the embodiment of FIG. 2, probe38 includes conduits 104 and 108 extending from chamber 18 a torespective connectors 112 and 116, as shown. In this embodiment,connectors 112 and 116 can be coupled to a pump to circulate liquidthrough chamber 18 a (e.g., and through a heat exchanger. For example,in some embodiments, pulse-generation system 26 (FIG. 1) can comprise apump and a heat exchanger in series and configured to be coupled toconnectors 112 and 116 via conduits or the like. In some embodiments, afilter can be included in probe 38 a, in a spark generation system(e.g., 26), and/or between the probe and the spark generation system tofilter liquid that is circulated through the chamber

Additionally, due to the limited life of electrodes 100 at high pulserates, some embodiments of the present probes may be disposable.Alternatively, some embodiments are configured to permit a user toreplace the electrodes. For example, in the embodiment of FIG. 2, sparkhead 22 a is configured to be removable from probe 38 a. For example,spark head 22 a may be removable through handle 50 a, or handle 50 a maybe removably coupled (e.g., via threads or the like) to head 46 a suchthat upon removal of handle 50 a from head 46, spark head 22 a can beremoved from head 46 a and replaced.

As illustrated in FIG. 2, application of each shockwave to a targettissue includes a wavefront 118 propagating from outlet 20 a andtraveling outward through tissue 74. As shown, wavefront 74 is curvedaccording to its expansion as it moves outwardly and partially accordingto the shape of the outer surface of outlet member 70 a that contactstissue 74. In other embodiments, such as that of FIG. 1, the outer shapeof the contact member can be planar or otherwise shaped to affectcertain properties of the wavefront as it passes through outlet 20 a andpropagates through the target tissue.

FIG. 2A depicts an enlarged cross-sectional view of first embodiment ofa removable spark head or module 22 a. In the embodiment shown, sparkhead 22 a comprises a sidewall 120 defining a spark chamber 124, and aplurality of electrodes 100 a, 100 b, 100 c disposed in the sparkchamber. In the embodiment shown, spark chamber 124 is filled withliquid 128 which may be similar to liquid 54 (FIG. 1). At least aportion of sidewall 120 comprises an acoustically permeable ortransmissive material (e.g., a polymer such as polyethylene) configuredto permit sound waves and/or shockwaves generated at the electrodes totravel through sidewall 120 and through chamber 18 a. For example, inthe embodiment shown, spark head 22 a includes a cup-shaped member 132that may be configured to be acoustically reflective and an acousticallypermeable cap member 136. In this embodiment, cap member 136 is domeshaped to approximate the curved shape of an expanding wavefront thatoriginates at the electrodes and to compress the skin when applied withmoderate pressure. Cap member 136 can be coupled to cup-shaped member132 with an O-ring or gasket 140 and a retaining collar 144. In theembodiment shown, cup-shaped member 132 has a cylindrical shape with acircular cross-section (e.g., with a diameter of 2 inches or less). Inthis embodiment, cup-shaped member includes bayonet-style pins 148, 152configured to align with corresponding grooves in head 46 a of probe 38a (FIG. 2) to lock the position of spark head 22 a relative to theprobe.

In the embodiment shown, an electrode core 156 having conductors 160 a,160 b, 160 c and extending through aperture 164, with the interfacebetween aperture 164 and electrode core 156 sealed with a grommet 168.In the embodiment shown, a central conductor 160 a extends through thecenter of core 156 and serves as a ground to corresponding centerelectrode 100 a. Peripheral conductors 160 b, 160 c are in communicationwith peripheral electrodes 100 b, 100 c to generate sparks across thespark gap between electrodes 100 a and 100 b, and between electrodes 100a and 100 c. It should be understood that while two spark gaps areshown, any number of spark gaps may be used, and may be limited only bythe spacing and size of the spark gaps. For example, other embodimentsinclude 3, 4, 5, 6, 7, 8, 9, 10, or even more spark gaps.

FIG. 2B depicts an enlarged cutaway side view of a second embodiment ofa removable spark head or module 22 b. In the embodiment shown, sparkhead or module 22 b comprises a sidewall 120 a defining a spark chamber124 a, and a plurality of electrodes 100 d-1, 100 d-2, 100, 100 fdisposed in the spark chamber. In the embodiment shown, spark chamber124 a is filled with liquid 128 a which may be similar to liquid 128and/or 54. At least a portion of sidewall 120 a comprises anacoustically permeable or transmissive material (e.g., a polymer such aspolyethylene) configured to permit sound waves and/or shockwavesgenerated at the electrodes to travel through sidewall 120 a and throughchamber 18 a (FIG. 2). For example, in the embodiment shown, spark head22 b includes a cup-shaped member 132 a that may be configured to beacoustically reflective and an acoustically permeable cap member 136 a.In this embodiment, cap member 136 a is dome shaped to approximate thecurved shape of an expanding wavefront that originates at the electrodesand to compress the skin when applied with moderate pressure. Cap member136 a can be coupled to cup-shaped member 132 a with an O-ring or gasket(not shown, but similar to 140) and a retaining collar 144 a. In theembodiment shown, cup-shaped member 132 a has a cylindrical shape with acircular cross-section (e.g., with a diameter of 2 inches or less. Insome embodiments, cup-shaped member can also include bayonet-style pins(not shown, but similar to 148, 152) configured to align withcorresponding grooves in head 46 a of probe 38 a to lock the position ofspark head 22 b relative to the probe.

In the embodiment shown, conductors 160 d, 160 e, 160 f extendingthrough a rear portion (opposite outlet cap member 136 a) of sidewall132 a, as shown. In this embodiment, central conductor 160 b andperipheral conductors 160 a, 160 c can be molded into sidewall 120 asuch that grommets and the like are not necessary to seal the interfacebetween the sidewall and the conductors. In the embodiment shown, acentral conductor 160 d serves as a ground to corresponding centerelectrodes 100 d-1 and 100 d-2, which are also in electricalcommunication with each other. Peripheral conductors 160 e, 160 f are incommunication with peripheral electrodes 100 e, 100 f to generate sparksacross the spark gap between electrodes 100 d-1 and 100 e, and betweenelectrodes 100 d-2 and 100 f. It should be understood that while twospark gaps are shown, any number of spark gaps may be used, and may belimited only by the spacing and size of the spark gaps. For example,other embodiments include 3, 4, 5, 6, 7, 8, 9, 10, or even more sparkgaps.

In the embodiment shown, central electrodes 100 d-1 and 100 d-2 arecarried by, and may be unitary with, an elongated member 172 extendinginto chamber 124 a toward cap member 136 a from sidewall 120 a. In thisembodiment, member 172 is mounted to a hinge 176 (which is fixedrelative to sidewall 120 a) to permit the distal end of the member(adjacent electrodes 100 d-1, 100 d-2 to pivot back and forth betweenelectrodes 100 e and 100 f, as indicated by arrows 180. In theembodiment shown, the distal portion of member 172 is biased towardelectrode 100 e by spring arms 184. In this embodiment, spring arms 184are configured to position electrode 100 d-1 at an initial spark gapdistance from electrode 100 e. Upon application of an electricalpotential (e.g., via a pulse-generation system, as described elsewherein this disclosure) across electrodes 100 d-1 and 100 e, a spark willarc between these two electrodes to release an electric pulse tovaporize liquid between these two electrodes. The expansion of vaporbetween these two electrodes drives member 172 and electrode 100 d-2downward toward electrode 100 f. During the period of time in whichmember 172 travels downward, the pulse-generation system can re-chargeand apply an electric potential between electrodes 100 d-2 and 100 f,such that when the distance between electrodes 100 d-2 and 100 f becomessmall enough, a spark will arc between these two electrodes to releasethe electric pulse to vaporize liquid between these two electrodes. Theexpansion of vapor between electrodes 100 d-2 and 100 f then drivesmember 172 and electrode 100 d-1 upward toward electrode 100 e. Duringthe period of time in which member 172 travels upward, thepulse-generation system can re-charge and apply an electric potentialbetween electrodes 100 d-1 and 100 e, such that when the distancebetween electrodes 100 d-1 and 100 e becomes small enough, a spark willarc between these two electrodes to release the electric pulse andvaporize liquid between these two electrodes, causing the cycle to beginagain. In this way, member 172 oscillates between electrodes 100 e and100 f until the electric potential ceases to be applied to theelectrodes.

The exposure to high-rate and high-energy electric pulses, especially inliquid, subjects the electrodes to rapid oxidation, erosion, and/orother deterioration that can vary the spark gap distance betweenelectrodes if the electrodes are held in fixed positions (e.g.,requiring electrodes to be replaced and/or adjusted). However, in theembodiment of FIG. 2B, the pivoting of member 172 and electrodes 100d-1, 100 d-2 between electrodes 100 e and 100 f effectively adjusts thespark gap for each spark. In particular, the distance between electrodesat which current arcs between the electrodes is a function of electrodematerial and electric potential. As such, once the nearest surfaces(even if eroded) of adjacent electrodes (e.g., 100 d-1 and 100 e) reacha spark gap distance for a given embodiment, a spark is generatedbetween the electrodes. As such, member 172 is configured to self-adjustthe respective spark gaps between electrodes 100 d-1 and 100 e, andbetween electrodes 100 d-2 and 100 f.

Another example of an advantage of the present movable electrodes, as inFIG. 2B, is that multiple coils are not required as long as theelectrodes are positioned such that only one pair of electrodes iswithin arcing distance at any given time, and such a single coil or coilsystem is configured to recharge in less time than it takes for member172 to pivot from one electrode to the next. For example, in theembodiment of FIG. 2B, an electric potential may simultaneously beapplied to electrodes 100 e and 100 f with electrodes 100 d-1 and 100d-2 serving as a common ground, with the electric potential such that aspark will only arc between electrodes 100 d-1 and 100 e when member 172is pivoted upward relative to horizontal (in the orientation shown), andwill only arc between electrodes 100 d-2 and 100 f when member 172 ispivoted downward relative to horizontal. As such, as member 172 pivotsupward and downward as described above, a single coil or coil system canbe connected to both of peripheral electrodes 100 e, 100 f andalternately discharged through each of the peripheral electrodes. Insuch embodiments, the pulse rate can be adjusted by selecting thephysical properties of member 172 and spring arms 184. For example, theproperties (e.g., mass, stiffness, cross-sectional shape and area,length, and/or the like) of member 172 and the properties (e.g., springconstant, shape, length, and/or the like) of spring arms 184 can bevaried to adjust a resonant frequency of the system, and thereby thepulse rate of the spark head or module 22 b. Similarly, the viscosity ofliquid 128 a may be selected or adjusted (e.g., increased to reduce thespeed of travel of arm 172, or decreased to increase the speed of travelof arm 172).

Another example of an advantage of the present movable electrodes, as inFIG. 2B, is that properties (e.g., shape, cross-sectional area, depth,and the like) of the electrodes can be configured to achieve a knowneffective or useful life for the spark head (e.g., one 30-minutetreatment) such that spark head 22 b is inoperative or of limitedeffectiveness after that designated useful life. Such a feature can beuseful to ensure that the spark head is disposed of after a singletreatment, such as, for example, to ensure that a new, sterile sparkhead is used for each patient or area treated to minimize potentialcross-contamination between patients or areas treated.

FIG. 2C depicts an enlarged cutaway side view of a third embodiment of aremovable spark head or module 22 c. Spark head 22 c is substantiallysimilar to spark head 22 b, except as noted below, and similar referencenumerals are therefore used to designate structures of spark head 22 cthat are similar to corresponding structures of spark head 22 b. Theprimary difference relative to spark head 22 b is that spark head 22 cincludes a beam 172 a that does not have a hinge, such that flexing ofthe beam itself provides the movement of electrodes 100 d-1 and 100 d-2in the up and down directions indicated by arrows 180, as describedabove for spark head 22 b. In this embodiment, the resonant frequency ofspark head 22 c is especially dependent on the physical properties(e.g., mass, stiffness, cross-sectional shape and area, length, and/orthe like) of beam 172 a. As described for spring arms 184 of spark head22 b, beam 172 a is configured to be biased toward electrode 100 e, asshown, such that electrode 100 d-1 is initially positioned at an initialspark gap distance from electrode 100 e. The function of spark head 22 cis similar to the function of spark head 22 b, with the exception thatbeam 172 a itself bends and provides some resistance to movement suchthat hinge 176 and spring arms 184 are unnecessary.

In the embodiment shown, spark head 22 b also includes liquid connectorsor ports 188, 192 via which liquid can be circulated through sparkchamber 124 b. In the embodiment shown, a proximal end 196 of spark head22 b serves as a combined connection with two lumens for liquid(connectors or ports 188, 192) and two or more (e.g., three, as shown)electrical conductors (connectors 160 d, 160 e, 160 f). In suchembodiments, the combined connection of proximal end 196 can be coupled(directly or via a probe or handpiece) to a combined tether or cablehaving two liquid lumens (corresponding to connectors or ports 188,192), and two or more electrical conductors (e.g., a first electricalconductor for connecting to connector 160 d and a second electricalconductor for connecting to both peripheral connectors 160 e, 160 f).Such a combined tether or cable can couple the spark head (e.g., and aprobe or handpiece to which the spark head is coupled) to apulse-generation system having a liquid reservoir and pump such that thepump can circulate liquid between the reservoir and the spark chamber.In some embodiments, cap member 136 a is omitted such that connectors orports 188, 192 can permit liquid to be circulated through a largerchamber (e.g., 18 a) of a handpiece to which the spark head is coupled.Likewise, a probe or handpiece to which spark head 22 a is configured tobe coupled can include electrical and liquid connectors corresponding tothe respective electrical connectors (160 d, 160 e, 160 f) and liquidconnectors (188, 192) of the spark head such that the electrical andliquid connectors of the spark head are simultaneously connected to therespective electrical and liquid connectors of the probe or handpiece asthe spark module is coupled to the handpiece (e.g., via pressing thespark head and probe together and/or a twisting or rotating the sparkhead relative probe).

In the present embodiments, a pulse rate of a few Hz to many KHz (e.g.,up to 5 MHz) may be employed. Because the fatiguing event produced by aplurality of pulses, or shockwaves, is generally cumulative at higherpulse rates, treatment time may be significantly reduced by using manymoderately-powered shockwaves in rapid succession rather than a fewhigher powered shockwaves spaced by long durations of rest. As notedabove, at least some of the present embodiments (e.g., those withmultiple spark gaps) enable electro-hydraulic generation of shockwavesat higher rates. For example, FIG. 3A depicts a timing diagram enlargedto show only two sequences of voltage pulses applied to the electrodesof the present embodiments, and FIG. 3B depicts a timing diagram showinga greater number of voltage pulses applied to the electrodes of thepresent embodiments.

In additional embodiments that are similar to any of spark modules 22 a,22 b, 22 c, a portion of the respective sidewall (120, 120 a, 120 b) maybe omitted such that the respective spark chamber (124, 124 a, 124 b) isalso omitted or left open such that liquid in a larger chamber (e.g., 18or 18 a) of a corresponding handpiece can freely circulate between theelectrodes. In such embodiments, the spark chamber (e.g., sidewall 120,120 a, 120 b can include liquid connectors or liquid may circulatethrough liquid ports that are independent of spark chamber (e.g., asdepicted in FIG. 2).

The portion of pulse train or sequence 200 shown in FIG. 3A includespulse groups 204 and 208 timed with a delay period 212 in between.Bursts or groups (e.g., 204, 208) may include as few as one or two, oras many as thousands, of pulses. In general, each group 204, 208 caninclude several voltage pulses that are applied to the electrodes totrigger an event (i.e., a spark across a spark gap). The duration ofdelay period 212 can be set to allow cooling of the electrodes acrosseach spark gap and to allow recharging of the electronics. As used forthe embodiments of this disclosure, pulse rate refers to the rate atwhich voltage pulse groups (each having one or more pulses) are appliedto the electrodes; meaning that individual pulses within pulse groupshaving two or more pulses are applied at a greater frequency, asillustrated in FIGS. 3A-3B. Each of these pulse groups can be configuredto generate one shock wave or a plurality of shock waves.

A series of events (sparks) initiated by a plurality of bursts or groups204 and 208 delivered with the present systems and apparatuses cancomprise a higher pulse rate (PR) that can reduce treatment timerelative to lower PRs which may need to be applied over many minutes.Tattoos, for example, may encompass broad areas and therefore are timeconsuming to treat unless rapid cell destruction is achieved (e.g., withthe higher PRs of the present disclosure). In contrast to the prior artsystems noted above, the present embodiments can be configured todeliver shock waves at a relatively high PR 216 of 10 to 5000 or morepulses per second (e.g., greater than any one of, or between any two of:10 Hz, 30 Hz, 50 Hz, 1000 Hz, 10000 Hz, 1000000 Hz, 500000 Hz, and/or5000000.

FIG. 4 depicts a waveform that can emitted by either of probes 38 or 38a into a volume of tissue, and that is of a form that can be useful forthe elimination of tattoos. Pulse 300 is of a typical shaped for animpulse generated by the present EH spark heads at relativelyhigh-voltage pulses. For example, pulse 300 has a rapid rise time, ashort duration, and a ring down period. The units of vertical axis V_(a)are arbitrary as may be displayed on an oscilloscope. The actualacoustic pulse amplitude may be as low as 50 μPa and as high as severalMPa in various ones of the present embodiments, at least becausecumulative energy delivery may be effective, as discussed above. Theindividual time periods 304 may be 100 nano-seconds each, whichcorresponds to short pulse lengths referred to in the art as “shockwave”pulses, owing to their sharpness and short rise and fall times. Forexample, a rise time of <30 nanoseconds is considered to be a shockwavefor purposes of the present disclosure, the rapidity being particularlyeffective for producing relative large pressure-temporal pressuregradients across small, cellular-scaled structures in tissue (e.g., thedermis). Rapid compression and decompression of dermal structurescontaining tattoo “inks” which are actually particulate pigments,results in a fatiguing and destruction of the pigment-containing cellsover time and is believed to be one underlying mechanism of the presentmethods, as described above. For example, agitation of tissue with suchshock waves has been shown to be effective, when applied at high pulserates within a relatively short time period, and at sufficient energylevels to produce a pigmented cell to rupture, with resulting liberationof entrapped particulates and subsequent dissemination of the pigmentparticles into the body, thereby reducing the appearance of the tattoo.It is believed to be necessary to have a short pulse waveform 300, whichmay be applied multiple times and preferably many hundreds to millionsof times to an area to be treated to produce the fatigue needed fortattoo “ink” removal.

FIG. 5 depicts a schematic diagram of one embodiment 400 of apulse-generation system for use in or with some embodiments of thepresent systems. In the embodiment shown, circuit 400 comprises aplurality of charge storage/discharge circuits each with a magneticstorage or induction type coil 404 a, 404 b, 404 c (e.g., similar tothose used in automotive ignition systems). As illustrated, each ofcoils 404 a, 404 b, 404 c, may be grounded via a resistor 408 a, 408 b,408 c to limit the current permitted to flow through each coil, similarto certain aspects of automotive ignition systems. Resistors 408 a, 408b, 408 c can each comprise dedicated resistors, or the length andproperties of the coil itself may be selected to provide a desired levelof resistance. The use of components of the type used automotiveignition systems may reduce costs and improve safety relative to customcomponents. In the embodiment shown, circuit 400 includes a spark head22 b that is similar to spark head 22 a with the exceptions that sparkhead 22 b includes three spark gaps 412 a, 412 b, 412 c instead of two,and that each of the three spark gaps is defined by a separate pair ofelectrodes rather than a common electrode (e.g., 100 a) cooperating withmultiple peripheral electrodes. It should be understood that the presentcircuits may be coupled to peripheral electrodes 100 b, 100 c of sparkhead 22 a to generate sparks across the spark gaps defined with commonelectrode 22 a, as shown in FIG. 2A. In the embodiment shown, eachcircuit is configured to function similarly. For example, coil 404 a isconfigured to collect and store a current for a short duration suchthat, when the circuit is broken at switch 420 a, the magnetic field ofthe coil collapses and generates a so-called electromotive force, orEMF, that results in a rapid discharge of capacitor 424 a across sparkgap 412 a.

The RL or Resistor-Inductance time constant of coil 404 a—which may beaffected by factors such as the size and inductive reactance of thecoil, the resistance of the coil windings, and other factors—generallycorresponds to the time it takes to overcome the resistance of the wiresof the coil and the time to build up the magnetic field of the coil,followed by a discharge which is controlled again by the time it takesfor the magnetic field to collapse and the energy to be released throughand overcome the resistance of the circuit. This RL time constantgenerally determines the maximum charge-discharge cycle rate of thecoil. If the charge-discharge cycle is too fast, the available currentin the coil may be too low and the resulting spark impulse weak. The useof multiple coils can overcome this limitation by firing multiple coilsin rapid succession for each pulse group (e.g., 204, 208 as illustratedin FIG. 3A). For example, two coils can double the practicalcharge-discharge rate by doubling the (combined) current and resultingspark impulse, and three (as shown) can effectively triple the effectivecharge-discharge rate. When using multiple spark gaps, timing can bevery important to proper generation of spark impulses and resultingliquid vaporization and shockwaves. As such, a controller (e.g.,microcontroller, processer, FPGA, and/or the like) may be coupled toeach of control points 428 a, 428 b, 428 c to control the timing of theopening of switches 420 a, 420 b, 420 c and resulting discharge ofcapacitors 424 a, 424 b, 424 c and generation of shockwaves.

FIG. 6 depicts a block diagram of an embodiment 500 of a radio-frequency(RF) powered acoustic shockwave generation system. In the embodimentshown, system 500 comprises a nonlinear medium 504 (e.g., as inacoustic-delay chamber 58 or nonlinear member described above) thatprovides an acoustic path to from a transducer 508 to target tissue 512to produce practical harmonic or acoustic energy (e.g., shockwaves). Inthe embodiment shown, transducer 508 is powered and controlled throughbandpass filter and tuner 516, RF power amplifier 520, and controlswitch 524. The system is configured such that actuation of switch 524activates a pulse generator 528 to produce timed RF pulses that driveamplifier 520 in a predetermined fashion. A typical driving waveform,for example, may comprise a sine wave burst (e.g., multiple sine wavesin rapid succession). For example, in some embodiments, a typical burstmay have a burst length of 10 milliseconds and comprise sine waveshaving a period duration of 0.1 (frequency of 100 MHz) to more than 2microseconds (frequency of 50 kHz).

Embodiments of the present methods comprise positioning an embodiment ofthe present apparatuses (e.g., 10, 38, 38 a, 500) adjacent to a regionof a patient comprising target cells (e.g., tissue 74); and activatingthe spark generation (e.g., capacitive/inductive coil) system (e.g., 26,400) to propagate shockwaves to the target cells. In some embodiments,the region is viewed through a window (e.g., 82, 82 a) while positioningthe apparatus and/or while the shockwaves are generated and delivered tothe region. Some embodiments further comprise coupling a removable sparkhead or module (e.g., 22 a, 22 b) to a housing of the apparatus prior toactivating the pulse-generation system.

Experimental Results

Experiments were conducted on tattooed skin samples obtained fromdeceased primates to observe effects of EH-generated shock waves ontattooed skin. FIGS. 7A-7B and 8 depict two different prototype sparkchamber housings. The embodiment of FIGS. 7A-7B depict a firstembodiment 600 of a spark chamber housing that was used in the describedexperiments. Housing 600 is similar in some respects to the portion ofhousing 14 a that defines head 46 a of probe 38 a. For example, housing600 includes fittings 604, 608 to permit liquid to be circulated throughspark chamber 612. In the embodiment shown, housing 600 includeselectrode supports 616 and 620 through which electrodes 624 can beinserted to define a spark gap 628 (e.g., of 0.127 millimeters or 0.005inches in the experiments described below). However, housing 600 has anelliptical inner surface shaped to reflect the shockwaves that initiallytravel backwards from the spark gap into the wall. Doing so has theadvantage of producing, for each shockwave generated at the spark gap, afirst or primary shockwave that propagates from the spark gap to outlet640, followed by a secondary shock wave that propagates first to theelliptical inner wall and is then reflected back to outlet 640.

In this embodiment, supports 616 and 620 are not aligned with (rotatedapproximately 30 degrees around chamber 612 relative to) fittings 604,608. In the embodiment shown, housing 600 has a hemispherical shape andelectrodes 624 are positioned such that an angle 632 between a centralaxis 636 through the center of shockwave outlet 640 and a perimeter 644of chamber 612 is about 57 degrees. Other embodiments can be configuredto limit this angular sweep and thereby direct the sound waves and/orshockwaves through a smaller outlet. For example, FIG. 8 depicts across-sectional view of a second embodiment 600 a of a spark chamberhousing. Housing 600 a is similar to housing 600, with the exceptionthat fittings 604 a, 608 a are rotated 90 degrees relative to supports616 a, 620 a. Housing 600 a also differs in that chamber 612 a includesa hemispherical rear or proximal portion and a frusto-conical forward ordistal portion. In this embodiment, electrodes 624 a are positioned suchthat such that an angle 632 a between a central axis 636 a through thecenter of shockwave outlet 640 a and a perimeter 644 a of chamber 612 ais about 19 degrees.

FIG. 9 depicts a schematic diagram of an electric circuit for a protypedpulse-generation system used with the spark chamber housing of FIGS.7A-7B in the present experimental procedures. The schematic includessymbols known in the art, and is configured to achieve pulse-generationfunctionality similar to that described above. The depicted circuit iscapable of operating in the relaxation discharge mode with embodimentsof the present shockwave heads (e.g., 46, 46 a, etc.). As shown, thecircuit comprises a 110V alternating current (AC) power source, anon-off switch, a timer (“control block”), a step-up transformer that hasa 3 kV or 3000V secondary voltage. The secondary AC voltage is rectifiedby a pair of high voltage rectifiers in full wave configuration. Theserectifiers charge a pair of oppositely polarized 25 mF capacitors thatare each protected by a pair of resistors (100 kΩ and 25 kΩ) inparallel, all of which together temporarily store the high-voltageenergy. When the impedance of the shockwave chamber is low and thevoltage charge is high, a discharge begins, aided by ionizationswitches, which are large spark gaps that conduct when the thresholdvoltage is achieved. A positive and a negative voltage flows to each ofthe electrodes so the potential between the electrodes can be up toabout 6 kV or 6000 V. The resulting spark between the electrodes resultsin vaporization of a portion of the liquid into a rapidly-expanding gasbubble, which generates a shock wave. During the spark, the capacitorsdischarge and become ready for recharge by the transformer andrectifiers. In the experiments described below, the discharge was about30 Hz, regulated only by the natural rate of charge and discharge—hencethe term “relaxation oscillation.” In other embodiments, the dischargerate can be as higher (e.g., as high as 100 Hz, such as for themulti-gap configuration of FIG. 5.

A total of 6 excised, tattooed primate skin samples were obtained, andspecimens were segregated, immobilized on a substrate, and placed in awater bath. A total of 4 tattooed specimens and 4 non-tattooed specimenswere segregated, with one each of the tattooed and non-tattooedspecimens held as controls. Shock chamber housing 600 was placed overeach of the excised specimens and voltage pulses applied to electrodes624 at full power for various durations. Shockwaves were generated at avoltage of about 5-6 kV and about 10 mA, which resulted in a power levelof about 50 W per pulse, and the shockwaves were delivered a rate ofabout 10 Hz. For purposes of the described experiments, multiple periodsof exposure were used and the results observed after the cumulativeperiods of exposure (e.g., cumulative total time of 10-20 minutes) asindicative of a longer period of exposure and/or a period of exposure ata greater pulse rate. The immediate results observed in the water bathshowed a formation of coagulum around the edge of the samples, which wasbelieved to indicate the flow of residual blood from the repeated shockwaves. All specimens were put into formalin for histopathology. Ahistopathologist reported an observed disruption of cell membranes and adispersal of the tattoo particles for tattoo pigment-containingmacrophages in the treated tissue. Changes to adjacent tissue—such asthermal damage, rupture of basal cells or formation of vacuoles—were notobserved. The specimen showing the most obvious disruption, which couldbe readily seen by an untrained eye, had the highest shock wave exposuretime duration of the group. This is strongly suggestive of a thresholdeffect that could be further illustrated as power and/or time areincreased.

Additional in-vitro monkey, and in-vivo monkey and porcine, tests weresubsequently performed using a further embodiment 38 b of the present(e.g., handheld) probes for use with some embodiments of the present EHshockwave generating systems and apparatuses depicted in FIGS. 11-13C.Probe 38 b is similar in some respects to probes 38 and 38 a, and thedifferences are therefore primarily described here. In this embodiment,probe 38 b comprises: a housing 14 b defining a chamber 18 b and ashockwave outlet 20 b; a liquid (54) disposed in chamber 18 b; aplurality of electrodes (e.g., in spark head or module 22 d) configuredto be disposed in the chamber to define one or more spark gaps; and isconfigured to be coupled to a pulse-generation system 26 configured toapply voltage pulses to the electrodes at a rate of between 10 Hz and 5MHz.

In the embodiment shown, spark head 22 d includes a sidewall or body 120d and a plurality of electrodes 100 g that define a spark gap. In thisembodiment, probe 38 b is configured to permit liquid to be circulatedthrough chamber 18 b via liquid connectors or ports 112 b and 116 b, oneof which is coupled to spark head 22 d and the other of which is coupledto housing 14 b, as shown. In this embodiment, housing 14 b isconfigured to receive spark head 22 d, as shown, such that housing 14 band sidewall or body 120 d cooperate to define chamber 18 b (e.g., suchthat spark head 22 d and housing 14 b include a complementary parabolicsurfaces that cooperate to define the chamber). In this embodiment,housing 14 b and spark head 22 d includes acoustically-reflective liners700, 704 that cover their respective surfaces that cooperate to definechamber 18 b. In this embodiment, sidewall or body 120 d of spark head22 d includes a channel 188 b (e.g., along a central longitudinal axisof spark head 22 d) extending between liquid connector 112 b and chamber18 b and aligned with the spark gap between electrodes 100 g such thatcirculating water will flow in close proximity and/or through the sparkgap. In the embodiment shown, housing 14 b includes a channel 192 bextending between connection 116 b and chamber 18 b. In this embodiment,spark head 22 d includes a groove 708 configured to receive a resilientgasket or O-ring 140 a to seal the interface between spark head 22 d andhousing 14 b, and housing 14 b includes a groove 712 configured toreceive a resilient gasket or O-ring 140 b to seal the interface betweenhousing 14 b and cap member 136 b when cap member 136 b is secured tohousing 14 b by ring 716 and retaining collar 144 b.

In the embodiment shown, electrodes 100 g each includes a flat barportion 724 and a perpendicular cylindrical portion 728 (e.g.,comprising tungsten for durability) in electrical communication (e.g.,unitary with) bar portion 724 such that cylindrical portion 728 canextend through a corresponding opening 732 in spark head 22 d intochamber 18 b, as shown. In some embodiments, part of the sides ofcylindrical portion 728 can be covered with an electrically insulativeand/or resilient material (e.g., shrink wrap) such as, for example, toseal the interface between portion 728 and housing 120 b. In thisembodiment, housing 120 b also includes longitudinal grooves 732configured to receive bar portions 724 of electrodes 100 g. In theembodiment shown, housing 38 g also includes set screws 736 positionedalign with cylindrical portions 732 of electrodes 100 g when spark head22 d is disposed in housing 38 g, such that set screws 736 can betightened to press cylindrical portions 736 inward to adjust the sparkgap between the cylindrical portions of electrodes 100 g. In someembodiments, spark head 22 d is permanently adhered to housing 38 b;however, in other embodiments, spark head 22 d may be removable fromhousing 38 b such as, for example, to permit replacement of electrodes100 g individually or as part of a new or replacement spark head 22 d.

FIG. 14 depicts a schematic diagram of a second embodiment of anelectric circuit for a prototyped pulse-generation system. The circuitof FIG. 14 is substantially similar to the circuit of FIG. 9 with theprimary exception that the circuit of FIG. 14 includes an arrangement oftriggered spark gaps instead of ionization switches, and includescertain components with different properties than correspondingcomponents in the circuit of FIG. 9 (e.g., 200 kΩ resistors instead of100 kΩ resistors). In the circuit of FIG. 14, block “1” corresponds to aprimary controller (e.g., processor) and block “2” corresponds to avoltage timer controller (e.g., oscillator), both of which may becombined in a single unit in some embodiments.

In the additional in-vitro monkey tests, probe 38 b of FIGS. 11-13C wasplaced over the tattoos of respective subjects and was powered by thecircuit of FIG. 14. In the monkey tests, voltage pulses were applied toelectrodes 100 g at varying frequencies (30-60 Hz) for varying durationsof one minute up to ten minutes. At the greatest power, shockwaves weregenerated at a voltage of about 0.5 kV (between a maximum of about +0.4kV and a minimum of about −0.1 kV) and a current of about 2300 A(between a maximum of about 1300 A and a minimum of about −1000 A),which resulted in a total power of about 500 kW per pulse and deliveredenergy of about 420 mJ per pulse, and the shockwaves were delivered arate of about 30 Hz. As with previous in-vitro tests, a histopathologistreported an observed disruption of cell membranes and a dispersal of thetattoo particles for tattoo pigment-containing macrophages in thetreated tissue. Changes to adjacent tissue—such as thermal damage,rupture of basal cells or formation of vacuoles—were not observed. Thespecimens showing the most obvious disruption were those with thehighest power and shock wave exposure time duration. These resultssuggested that increased power and increased number of shocks (resultingin an overall increase in delivered power) caused an increaseddisruption of pigments, which was consistent with the earlier in-vitrotests.

In the in-vivo tests, probe 38 b of FIGS. 11-13C was placed over thetattoos of respective subjects and was powered by the circuit of FIG.14. In the monkey tests, voltage pulses were applied to electrodes 100 gat full power for a duration of two minutes and repeated once per weekfor six weeks. Shockwaves were generated at a voltage of about 0.5 kV(between a maximum of about +0.4 kV and a minimum of about −0.1 kV) anda current of about 2300 A (between a maximum of about 1300 A and aminimum of about −1000 A), which resulted in a total power of about 500kW per pulse and delivered energy of about 420 mJ per pulse, and theshockwaves were delivered a rate of about 30 Hz. In-vivo porcine testswere similar, except that shockwaves were applied for duration of fourminutes at each application. One week after the sixth application ofshockwaves, biopsies were taken from each tattoo. All specimens were putinto formalin for histopathology. A histopathologist reported anobserved disruption of cell membranes and a dispersal of the tattooparticles for tattoo pigment-containing macrophages in the treatedtissue, with a relatively greater dispersal for specimens that underwent4-minute treatments than those that underwent 2-minute treatments.Changes to adjacent tissue—such as thermal damage, rupture of basalcells or formation of vacuoles—were not observed. These results wereconsistent with those observed for the in-vitro monkey tests. Overall,these studies suggested that increased power and increased number ofshocks (resulting in an overall increase in delivered power—e.g., due toincreased duration of treatment).

Methods

Examples of maladies and/or conditions that involve particlesagglomerated in cellular structures include cancer, crystallinemicro-particles in the musculoskeletal system, or removal of tattoos.These are merely no limiting exemplary conditions that can be treated oraddressed by rupturing or destruction of cells containing particleagglomerates. In some embodiments, destruction of the cells containingparticle agglomeration may be caused by non-thermal cell membranedegradation of the specific cells secondary to nonlinear processesaccompanying propagation of high frequency shock waves, as discussedabove.

Some general embodiments of the present methods comprise: delivering aplurality of electro-hydraulically generated (e.g., via one or more ofthe present apparatuses) shock waves to at least one cellular structurecomprising at least one region of heterogeneity until the at least onecellular structure ruptures. In some embodiments, the shock waves aredelivered for no more than 30 minutes in a 24-hour period. In someembodiments, the shock waves are delivered for no more than 20 minutesin a 24-hour period. In some embodiments, between 200 and 5000shockwaves are delivered in between 30 seconds and 20 minutes at each ofa plurality of positions of a shockwave outlet.

A. Tattoos

Tattoos are essentially phagocytosing cells such as fibroblast cells,macrophages, and the like that contain agglomerates of ink particles.Because the captured ink particles are denser than the biologicalstructures of the cells, tattoos or cells containing ink particles havea large difference in elasticity in its structure. When subject to shockwaves, the cells containing ink particles are subject to greatermechanical strain as compared to other cells that do not contain denseparticles. Shock waves can be configured to be delivered at an optimalfrequency and amplitude to accelerate the ink particles sufficiently torupture the particular cells while leaving intact fibroblast cells thatdo not have the particular elasticity difference. The details of tattoosand biological process of removal of released from cells are discussedfurther below.

Tattoo inks and dyes were historically derived from substances found innature and generally include a heterogeneous suspension of pigmentedparticles and other impurities. One example is India ink, which includesa suspension of carbon particles in a liquid such as water. Tattoos aregenerally produced by applying tattoo ink into the dermis, where the inkgenerally remains substantially permanently. This technique introducesthe pigment suspension through the skin by an alternatingpressure-suction action caused by the elasticity of the skin incombination with the up-and-down movement of a tattoo needle. Water andother carriers for the pigment introduced into the skin diffuse throughthe tissues and are absorbed. For the most part, 20%-50% of the pigmentis disseminated into the body. However, the remaining portion of theinsoluble pigment particles are deposited in the dermis where placed. Intattooed skin, pigment particles generally are phagocytized by cellsresulting in pigment agglomerates in the cytoplasm of the cells (i.e.,in the membrane-bound structures known as secondary lysosomes).Resulting pigment agglomerates (“particle agglomerates”) may range up toa few micrometers in diameter. Once the skin has healed, the pigmentparticles remain in the interstitial space of the skin tissue within thecells. Tattoo inks generally resist elimination due to the cellsimmobility due to the relatively large amount of insoluble pigmentparticles in the cells. A tattoo may fade over time, but will generallyremain through the life of the tattooed person.

Tattoo inks typically comprise aluminum (87% of the pigments), oxygen(73% of the pigments), titanium (67% of the pigments), and carbon (67%of the pigments). The relative contributions of elements to the tattooink compositions were highly variable between different compounds. Atleast one study has determined the particle size for three commercialtattoo inks as shown in Table 1:

TABLE 1 Tattoo Pigment Particle Size Color Mean Diameter Std deviationViper Red 341 nm 189 nm Agent Orange 228 nm 108 nm Hello yellow 287 nm153 nm

B. Tattoo Removal

In conventional tattooing (decorative, cosmetic, and reconstructive),once the pigment or dye has been administered into the dermis to form atattoo, the pigment or dye generally remains permanently in place, asdiscussed above.

Despite the general permanency of tattoos, individuals may wish tochange will remove tattoos for a variety of reasons. For example, overtime people may have a change of heart (or mind), and may desire toremove or change the design of a decorative tattoo. By way of anotherexample, an individual with cosmetic tattooing, such as eyeliners,eyebrows, or lip coloring, may wish to change the color or area tattooedas fashion changes. Unfortunately, there is currently no simple andsuccessful way to remove tattoos. Currently, methods of removingtraditional tattoos (e.g., pigment-containing skin) may includesalabrasion, cryosurgery, surgical excision, and CO2-laser. Thesemethods may require invasive procedures associated with potentialcomplications, such as infections, and usually results in conspicuousscarring. More recently, the use of Q-switched lasers has gained wideacceptance for the removal of tattoos. By restricting pulse duration,ink particles generally reach very high temperatures resulting in thedestruction of the tattoo ink pigment-containing cells with relativelyminimal damage to adjacent normal skin. This significantly decreases thescarring that often results after nonselective tattoo removal methods,such as dermabrasion or treatment with carbon dioxide laser. Themechanisms of tattoo removal by Q-switch laser radiation may still bepoorly understood. It is thought that Q-switch laser allow for morespecific removal of tattoos by the mechanisms of selectivephotothermolysis and thermokinetic selectivity. Specifically, it isthought that the pigment particles in cells are able to absorb the laserlight causing heating of the particles resulting thermal destruction ofthe cells containing said particles. The destruction of these cellsresults in the release of particles which can then be removed from thetissue through normal absorptive processes.

While the Q-switch laser may be better than some alternatives for theremoval of tattoos, it is not perfect. Some tattoos are resistant to alllaser therapies despite the predicted high particle temperaturesachieved through selective photothermolysis. Reasons cited for failureof some tattoos to clear include the absorption spectrum of the pigment,the depth of pigment, and structural properties of some inks. Adverseeffects following laser tattoo treatment with the Q-switched ruby lasermay include textural changes, scarring, and/or pigmentary alteration.Transient hypopigmentation and textural changes have been reported in upto 50 and 12%, respectively, of patients treated with the Q-switchedalexandrite laser. Hyperpigmentation and textural changes are infrequentadverse effects of the Q-switched Nd:YAG laser and the incidence ofhypopigmentary changes are generally lower than with the ruby laser. Thedevelopment of localized and generalized allergic reactions is alsoimpossible (even if unusual) complication of tattoo removal with theQ-switched ruby and Nd:YAG lasers. Additionally, laser treatment may bepainful, such that use of a local injection with lidocaine or topicalanesthesia cream typically is used prior to laser treatment. Finally,laser removal generally requires multiple treatment sessions (e.g., 5 to20) and may require expensive equipment for maximal elimination.Typically, since many wavelengths are needed to treat multicoloredtattoos, not one laser system can be used alone to remove all theavailable inks and combination of inks. Even with multiple treatments,laser therapy may only be able to eliminate 50-70% of the tattoopigment, resulting in a residual smudge.

Some embodiments of the present methods comprise: directingelectro-hydraulically generated shock waves (e.g., from an embodiment ofthe present apparatuses) to cells of a patient; where the shock wavesare configured to cause particles to rupture one or more of the cells.Some embodiments comprise: providing an embodiment of the presentapparatuses; actuating apparatus to former shockwaves configured tocause particles within a patient to rupture one or more cells of thepatient; and directing the shockwaves to cells of a patient such thatthe shockwaves cause particles to rupture one or more of the cells(e.g., such as by degradation of the cell wall or membrane). In someembodiments, the one or more shockwaves are configured to havesubstantially no lasting effect on cells in the absence of particles(e.g., configured to cause substantially no permanent or lasting damageto cells that are not close enough to particles to be damaged by theparticles in the presence of the shockwaves).

Some embodiments of the present methods comprise focusing the one ormore shockwaves a specific region of tissue that comprises the cells. Insome embodiments the region of tissue at which the one or moreshockwaves is focused is a depth beneath the patient's skin. Theshockwaves can be focused by any of a variety of mechanisms. Forexample, a surface of the present apparatuses that is configured tocontact a patient during use (e.g., of outlet member 70 a) may be shaped(e.g., convex) to focus or shaped (e.g., convex) to disperse shockwaves,such as, for example, to narrow the area to which shockwaves aredirected or expand the area to which shockwaves are directed. Focusingthe shockwaves may result in higher pressures at targeted cells, suchas, for example, pressures of 10 MPa, 15-25 MPa, or greater. In someembodiments, the convex outer shape is configured to tension a portionof a patient's skin as the outlet member is pressed against the skin.

Some embodiments of the present methods further comprise: identifyingtarget cells of the patient to be ruptured (e.g., prior to directing theone or more shockwaves to the target cells). In various embodiments, thetarget cells can comprise any of a variety of target cells, such as, forexample, target cells comprising a condition or malady involvingcellular particle agglomerates. For example, the target cells maycomprise: a tattoo, musculoskeletal cells comprising crystallinemicro-particles, hair follicles that contain keratin protein, dentalfollicles that contain enamel, cancer cells, and/or the like. By way ofanother example, target cells may comprise one or more skin maladiesselected from the group consisting of: blackheads, cysts, pustules,papules, and whiteheads.

In some embodiments, the particles can comprise non-natural particles.One example of non-natural particles includes tattoo pigment particles,such as are commonly disposed in the human dermis to create a tattoo. Insome embodiments, the pigments can comprise an element with anatomicnumber of less than 82. In some embodiments, the particles can compriseany one or combination of: gold, titanium dioxide, iron oxide, carbon,and/or gold. In some embodiments, the particles have a mean diameter ofless than 1000 nm (e.g., less than 500 nm and/or less than 100 nm).

FIG. 10 illustrates one embodiment of a method 700 of using apparatus 10to direct shockwaves to target tissue. In the embodiment shown, method700 comprises a step 704 in which target cells 708 of a patient's tissue712 are identified for treatment. For example, tissue 712 can compriseskin tissue, and/or target cells 708 can comprise cells containingtattoo pigment within or near skin tissue. In the embodiment shown,method 700 also comprises a step 716 in which a probe or handpiece 38 isdisposed adjacent tissue 712 and/or tissue 716, such that shockwavesoriginating in probe 38 can be directed toward the target cells 708. Inthe embodiment shown, method 700 also comprises a step 720 in which apulse-generation system 26 is coupled to probe 38. In the embodimentshown, method 700 also comprises a step 724 in which pulse-generationsystem 26 is activated to generate sparks across electrodes within probe38 to generate shockwaves in probe 38 for delivery to target cells 708,as shown. In the embodiment shown, method 700 also comprises an optionalstep 728 in which pulse-generation system 26 is de-coupled from probe38, and probe 38 is removed from or moved relative to tissue 712. In theembodiment shown, target cells 708 are omitted from step 728,representing their destruction. Other embodiments of the present methodsmay comprise some or all of the steps illustrated in FIG. 10.

C. Methods of Removing Tissue Markings

In some embodiments of the present methods of diminishing tissuemarkings (e.g., tattoos) caused by pigments in dermis tissue involve theuse of one of the present apparatuses. In such methods, high-frequencyshockwaves are transmitted to and into a patient's skin, such that whenthe shock waves generated from the apparatus of the present disclosurereach the dermal cells and vibrate or accelerate the intradermalparticles, these particles experience movement relative cell membranesthat can lead to fatigue degradation and rupturing of cells, therebyreleasing the pigment particles. Released particles can then be removedfrom the surrounding tissue through normal absorptive processes of thepatient's body. In some embodiments, one of the present apparatuses canbe disposed adjacent to, and/or such that the shock waves from theapparatus are directed to the tissue site having the tattoo, othertissue markings, or other cellular structures containing particleagglomerates. To cause particle alteration (e.g., cell degradationsufficient to release particles for absorption), the shock waves can bedelivered to a specific area for a period of time long enough to rupturecells containing and/or adjacent to the pigment particles such that thepigment particles are released. In some embodiments the presentapparatuses have a focus or effective area that may be relativelysmaller than a tattoo, such that the apparatus may be periodically andare sequentially focused are directed at different areas of a tattoo tocause a reduction in perceptible pigments over the entire area of thetattoo. For instance, the parameters of the embodiments of the apparatusdisclosed here can be modified to achieve the desire number of shocksdelivered to a particular site in a desired amount of time. Forinstance, in one embodiment, shock waves are produced from acousticwaves with frequency of at least 1 MHz according to aspects of thepresent disclosure and exposed to a particular treatment site for theappropriate period of time to deliver at least about 100, 200, 300, 400,500, or 1000 shock waves to the treatment site. The shock waves can bedelivered all at once or through intervals (e.g., bursts) of shock waves(such as 5, 10, 15, 20, 25, 30, 40, 50, etc. shock waves at a time). Theappropriate interval and time between the interval can be modifiedand/or determined to achieve the desired effect at the treatment site,e.g., rupture of the targeted cellular structures. It is understood thatif acoustic waves with higher frequency are used, such as 2 MHz, 3 MHz,4 MHz, or 5 MHz, the treatment time can be adjusted, likely shorterexposure time, to achieve the desired amount of shock waves delivered tothe treatment area.

As will be appreciated by those of ordinary skill in the art, inembodiments of the present methods for removing tattoos, the particlesaffected by the shock waves can comprise tattoo pigment (particles),such as may, for example, be at least partially disposed between and/orwithin skin cells of the patient. Such pigment particles may, forexample, include at least one or combination of any of the following:titanium, aluminum, silica, copper, chromium, iron, carbon, or oxygen.

The use of high frequency shock waves to remove or reduce skin markingshas many advantages over the use of lasers. For example, lasertreatments for tattoo removal may be very painful. In contrast,high-frequency shockwaves (e.g., ultrasound shockwaves) can beconfigured and/or applied such that tattoos or other skin markings maybe removed or diminished with little if any pain to the patient,especially, for example, where the shock waves are targeted or otherwiseconfigured to degrade only cells that contain tattoo pigments. By way ofanother example, laser light directed at tissue has been found to causedamage to or destruction of surrounding tissues; whereas high-frequencyshock waves may be applied so as to cause little damage or destructionof surrounding tissues (e.g., because non-tattooed surrounding tissuesgenerally lack tattoo pigment or other particles that might otherwiseinteract with neighboring cells to cause sell degradation). Finally,laser tattoo removal often requires multiple treatment sessions (e.g.,5-20 sessions) for maximal tattoo elimination, and/or often requires theuse of expensive equipment. Additionally, since many wavelengths a laserlight may be needed to remove multicolored tattoos, multiple lasersystems may be needed to remove the variety of available inks and/orcombinations of available inks. As a result, the overall cost of lasertattoo removal may be prohibitively expensive. Even with multipletreatments, laser therapy may be limited to eliminating only 50 to 70%of tattoo pigment, and may leave a residual “smudge.” In contrast,high-frequency shockwaves is not dependent upon the color of tattoopigments such that therapeutic application of high-frequency shockwavesdoes not require different apparatuses for different colors of pigment,and such that high-frequency shockwaves may be applied to a relativelylarge area (e.g., the entire area of a tattoo), thereby reducing thenumber of treatment sessions required to achieve a level of tattooremoval or reduction that is acceptable to the patient (e.g., 30, 40,50, 60, 70, 80, 90, 95, or more percent reduction in the perceivablepigment in the patient's skin).

In some embodiments, the present methods include the application ofhigh-frequency shockwaves (e.g. with one or more of the presentapparatuses) and the application of laser light. For example, someembodiments of the present methods further comprise directing a beam oflight from a Q-switched laser at the target cells (e.g., tattooed skin).In some embodiments, directing one or more shockwaves and directing thebeam of light are performed in alternating sequence.

In some embodiments, the present methods include delivering one or morechemical or biological agents (e.g., configured to aid in the removal oftissue markings such as tattoos) to a position at or near the targetcells before, after, and/or simultaneously with directing the one ormore shockwaves to the target cells. For example, some embodiments ofthe present methods further comprise applying a chemical or biologicalagent to the skin (e.g., before, after, and/or simultaneously withdirecting one or more shockwaves and/or a beam of laser light at theskin). Examples of chemical or biological agents include: chelators(e.g., ethylenediaminetetraacetic acid (EDTA)); immune modulators (e.g.,Imiquimod [5]); combinations thereof; and/or other suitable chemical inor biological agents. In various embodiments, chemical in or biologicalagents to be delivered transdermally and/or systemically (e.g., theinjection) to the target cells (e.g., may be applied topically totattooed skin).

Some embodiments of the present methods of tattoo removal includemultiple applications of shockwaves to tattooed skin tissue (e.g., for aduration of at least 1 second (e.g., 10 seconds, or more), once per weekfor 6 or more weeks).

D. Method of Treating Additional Maladies and Conditions

In addition to tattoo removal, embodiments of the present methods mayinclude the application of high-frequency shockwaves to treat a varietyof maladies under conditions caused by and/or including symptoms ofcellular particle agglomerates and/or particles disposed inintracellular spaces and/or interstitial spaces. For example, suchmaladies and/or conditions may include: crystal joint, ligament, tendonand muscle disease, and/or dermatological maladies involving particleagglomerates including acne, age spots, etc. Additionally, embodimentsof the present methods may include the application of high-frequencyshockwaves after delivering nanoparticles to a region of the patientthat includes the target cells. For example, in some embodiments,nanoparticles (e.g., gold nanoparticles) are delivered to a patient'sbloodstream intravenously and permitted to travel to a region of thepatient that includes the target cells (e.g. a cancerous tumor), suchthat high-frequency shockwaves can be directed to the target region tocause the nanoparticles to interact with and rupture the target cells.

Further, embodiments of the present apparatuses (e.g., apparatus 10) canbe used for wrinkle reduction. For example, some embodiments of thepresent methods of generating therapeutic shock waves, comprise:providing any of the present apparatuses (e.g., apparatus 10); andactuating the apparatus to generate one or more shock waves. Someembodiments further comprise: disposing the apparatus (e.g., outlet end34 of housing 18) adjacent tissue of a patient such that at least oneshock wave enters the tissue. In some embodiments, the tissue comprisesskin tissue on the face of the patient.

In embodiments of the present methods that include directing particles(e.g., micro-particles and/or nanoparticles) to a position at or nearthe target cells (prior to directing shockwaves to the cells), theparticles can comprise: silk, silk fibron, carbon nanotubes, liposomes,and/or gold nanoshells. For example, in some embodiments, directing theparticles can comprises injecting into the patient a fluid suspensionthat includes the particles. Include suspension may, for example,comprise saline and/or hyaluronic acid.

Deposition of crystals and other miscellaneous crystals in articular andparticular tissues can result in a number of disease states. Forexample, monosodium urate monohydrate (MSUM) deposition in a joint mayresults in gout. As another example, calcium pyrophosphate dehydrate(CPPD) in joint tissues and fluids may result in a number of diseaseconditions, such as, for example, chondrocalcinosis (i.e., presence ofcalcium-containing crystals detected as radiodensities in articularcartilage). By way of further example, hydroxyapatite (HA) crystaldeposition may result in calcific tendonitis and perarthritis. In someembodiments of the present methods, the particles may comprise naturalparticles (e.g., particles naturally occurring within the body), suchas, for example, crystalline micro-particles such as may be form and/orbecome disposed in the musculoskeletal system of a patient. Otherexamples of natural particles they may be treated and/or disbursed inthe present methods include: urate crystals, calcium-containingcrystals, and/or hydroxyapatite crystals.

In embodiments of the present methods for treatment of acne or otherskin-based conditions, the particles may comprise dirt and/or debristhat is disposed in one or more pores of the patient's skin, and/or maycomprise keratin protein disposed of the patient's skin. In embodimentsof the present methods of treating (e.g., pathological) conditionsassociated with bone and musculoskeletal environments and soft tissuesby applying shockwaves can induce localized trauma and cellularapoptosis (including micro-fractures), or may induce osteoblasticresponses such as cellular recruitment, stimulate formation of molecularbone, cartilage, tendon, fascia, and soft tissue morphogens and growthfactors, and/or may induce vascular neoangiogenesis.

Some embodiments of the present methods of treating tumors or othermaladies include multiple applications of shockwaves to targeted tissue(e.g., a tumor, an area of skin with acne or other conditions, etc.),such as, for example, for a duration of at least (e.g., 10 seconds, ormore), once per week for 6 or more weeks.

The above specification and examples provide a description of thestructure and use of exemplary embodiments. Although certain embodimentshave been described above with a certain degree of particularity, orwith reference to one or more individual embodiments, those skilled inthe art could make numerous alterations to the disclosed embodimentswithout departing from the scope of this invention. As such, the variousillustrative embodiments of the present devices are not intended to belimited to the particular forms disclosed. Rather, they include allmodifications and alternatives falling within the scope of the claims,and embodiments other than the one shown may include some or all of thefeatures of the depicted embodiment. For example, components may becombined as a unitary structure. Further, where appropriate, aspects ofany of the examples described above may be combined with aspects of anyof the other examples described to form further examples havingcomparable or different properties and addressing the same or differentproblems. Similarly, it will be understood that the benefits andadvantages described above may relate to one embodiment or may relate toseveral embodiments.

The claims are not intended to include, and should not be interpreted toinclude, means-plus- or step-plus-function limitations, unless such alimitation is explicitly recited in a given claim using the phrase(s)“means for” or “step for,” respectively.

REFERENCES

-   [1] Burov, V. A., Nonlinear ultrasound: breakdown of microscopic    biological structures and nonthermal impact on malignant tumor.    Doklady Biochemistry and Biophysics Vol. 383, pp. 101-104 (2002).-   [2] Delius, M., Jordan, M., & et al. (1988). Biological effects of    shock waves: Kidney Haemorrhage by shock waves in    dogs—administration rate dependence. Ultrasound in Med. & Biol.,    14(8), 689-694.-   [3] Fernandez, P. (15 May 2006). A master relation defines the    nonlinear viscoelasticity of single fibroblasts. Biophysical    journal, Vol. 90, Issue 10, 3796-3805.-   [4] Freund, J. B., Colonius, T., & Evan, A. P. (2007). A cumulative    shear mechanism for tissue damage initiation in shock-wave    lithotripsy. Ultrasound in Med & Biol, 33(9), 1495-1503.-   [5] Gillitzer, R., & et al. (2009). Low-frequency extracorporeal    shock wave lithotripsy improves renal pelvic stone disintegration in    a pig model. BJU Int, 176, 1284-1288.-   [6] Kasza, K. E. (2007). The cell as a material. Current Opinion in    Cell Biology 2007, 19:101-107.-   [7] Madbouly, K., & et al. (2005). Slow versus fast shock wave    lithotripsy rate for urolithiasis: a prospective randomized study.    The Journal of urology, 173, 127-130.

1. An apparatus associated with generation of therapeutic shock waves,the apparatus comprising: a spark housing configured to be removablycoupled to a probe, the spark housing including: a body that defines achamber having a shockwave outlet, the chamber configured to be filledwith a liquid; a first connector coupled to the body and configured tobe electrically coupled to the probe via a second connector of theprobe; and a plurality of electrodes disposed in the chamber andconfigured to define one or more spark gaps, at least one electrode ofthe plurality of electrodes electrically coupled to the first connector;where the spark housing is removable from the probe as a single unitthat includes the body, the first connector, and the plurality ofelectrodes.
 2. The apparatus of claim 1, where the spark housingcomprises a spark head and a first housing coupled to the spark head. 3.The apparatus of claim 2, where: the spark head defines a first portionof the chamber; and the first housing defines a second portion of thechamber, the first portion and the second portion cooperate to definethe chamber.
 4. The apparatus of claim 2, where spark head ispermanently adhered to the first housing.
 5. The apparatus of claim 1,where the spark housing further includes a first liquid connector influid communication with the chamber, the first liquid connectorconfigured to be coupled to a conduit of the probe to enable circulationof the liquid.
 6. The apparatus of claim 5, further comprising: theprobe including a first plurality of electrical connectors associatedwith the second connector of the probe and configured to be coupled to apulse-generation system; and where, the spark housing further includes asecond plurality of electrical connectors associated with the firstconnector of the spark housing and configured to be electrically coupledto the first plurality of electrical connectors of the probe.
 7. Theapparatus of claim 5, further comprising: the probe including: a handleportion; a high voltage connector positioned on the handle portion andcoupled to a pulse-generation system; and where the spark housing isconfigured to be couple to the pulse-generation system via the probe. 8.The apparatus of claim 5, where the plurality of electrodes include afirst electrode and a second electrode moveable relative to the firstelectrode, the first electrode and the second electrode defining a firstspark gap of the one or more spark gaps.
 9. The apparatus of claim 8,where, when the chamber is filled with the liquid and the spark housingis coupled to a pulse-generation system, the plurality of electrodes areconfigured to receive voltage pulses from the pulse-generation systemvia the first and second connectors such that portions of the liquid arevaporized to generate therapeutic shockwaves that propagate through theliquid and out the shockwave outlet.
 10. An apparatus associated withgeneration of therapeutic shockwaves, the apparatus comprising: a sparkhousing configured to be removably coupled to a hand-held probe, thespark housing comprising: a body defining a chamber and having: a firstend that defines an outlet of the chamber; and a second end that isopposite the first end, the second end configured to be removablycoupled to the probe; at least two electrodes disposed within thechamber, the at least two electrodes defining a first spark gapconfigured to generate one or more shockwaves that propagate through thechamber and out of the outlet; and a first electrical connector coupledto the body and configured to be electrically coupled to one or moresecond electrical connectors of the probe; and where the spark housingis removable from the probe as a single unit that includes the body, thefirst electrical connector, and the at least two electrodes.
 11. Theapparatus of claim 10, where when the chamber is filled with liquid andthe spark housing is coupled to a pulse-generation system, the at leasttwo electrodes are configured to receive voltage pulses from thepulse-generation system via the first and second electrical connectorssuch that portions of the liquid are vaporized to generate therapeuticshockwaves that propagate through the liquid and to the outlet.
 12. Theapparatus of claim 10, where the spark housing further includes a capmember coupled to the first end of the body.
 13. The apparatus of claim11, where the second end of the body defines a channel configured to bein communication with the probe while the spark housing is coupled tothe probe.
 14. The apparatus of claim 13, where the at least twoelectrodes are aligned with the channel.
 15. The apparatus of claim 13,where the spark housing further includes a first liquid connector influid communication with the chamber, the first liquid connectorconfigured to be coupled to a conduit of the probe to enable circulationof the liquid within the chamber.
 16. The apparatus of claim 11 furthercomprising: the probe including: a handle portion; a high voltageconnector positioned on the handle portion and coupled to thepulse-generation system; the second electrical connector coupled to thehandle portion; and where the spark housing is configured to be coupledto the pulse-generation system via the probe.
 17. A method comprising:generating a plurality of shockwaves, via a plurality of electrodesdisposed within a chamber of a first spark housing, the first sparkhousing including: a body defining the chamber and having: a first endthat defines a shockwave outlet of the chamber; and a second end that isopposite the first end, the second end configured to be removablycoupled to a handheld probe; the plurality of electrodes disposed withinthe chamber, the plurality of electrodes defining a first spark gap; anda first electrical connector coupled to the body and configured to beelectrically coupled to one or more second electrical connectors of theprobe; and propagating the plurality of shockwaves through the chamberand out of the shockwave outlet; where the spark housing is removablefrom the probe as a single unit that includes the body, the firstelectrical connector, and the plurality of electrodes.
 18. The method ofclaim 17, further comprising coupling the first spark housing to theprobe.
 19. The method of claim 17, further comprising decoupling thefirst spark housing from the probe.
 20. The method of claim 19, furthercomprising coupling a second spark module to the probe, the second sparkmodule including a second body defining a second chamber, a secondplurality of electrodes coupled to the second body, and a thirdelectrical connector configured to be electrically coupled to one ormore second electrical connectors of the probe.